Application form Research Project Proposal

KINGDOM OF SAUDI ARABIA

National Science, Technology and Innovation Plan

Page 1 of 25

Sohda, T, Momose, Y, Meguro, K, Kawamatsu, Y, Sugiyama, Y, Ikeda, H, Arzneim-Forsch, 1990, 40, 37.

http://apps.webofknowledge.com.ezproxy.lib.ucalgary.ca/DaisyOneClickSearch.do?product=WOS&search_mode=DaisyOneClickSearch&colName=WOS&SID=4DC7DBnPOo3AKCOL8ff&author_name=IKEDA,%20H&dais_id=1367700



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CNPSTI RE-D1: APPLICATION FORM - RESEARCH PROJECT PROPOSAL

ITEM DESCRIPTION

PLAN The First Five - Year Science, Technology and Innovation Plan

PROGRAM Strategic Technologies

SUB-PROGRAM /

TECHNOLOGY AREA1

Biotechnology

TRACK Medical and Health Research

SUB-TRACK Diabetics

PROJECT TITLE

(ENGLISH)

COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN,

SYNTHESIS AND ANTIDIABETIC EVALUATION OF NEW

POTENTIAL ANTIDIABETIC AGENTS

PROJECT TITLE

(ARABIC) . دوائى مبنى على النمذجة الجزيئية الحبسوبية وتشييد وتقييمتصميم

PRINCIPAL

INVESTIGATOR

(ENGLISH)

Dr. Noman Shah

P. INVESTIGATOR

(ARABIC ) نعمبن. د

INSTITUTION Umm Al-Qura University

FOR OFFICIAL USE ONLY

SUBMITTED FOR THE

DEADLINE OF 30

th of MARCH 30

th of SEPTEMBER

DATE RECIEVED

PROJECT CODE

1 Applicants are advised to visit the following link for more information about technology areas, tracks and sub-

tracks http://www.kacst.edu.sa/en/research/Pages/default.aspx.

http://www.kacst.edu.sa/en/research/Pages/default.aspx



Page 3 of 25

CNPSTI RE -D1-1: PROJECT INFORMATION

ITEM DESCRIPTION

PROJECT TITLE

COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN,

SYNTHESIS AND ANTIDIABETIC EVALUATION OF NEW POTENTIAL

ANTIDIABETIC MEDICINE

TECHNOLOGY

AREA

Biotechnology

TRACK Medical and Health Research

SUB-TRACK Diabetics

PROJECT TYPE

(BASIC, APPLIED,

DEVELOPMENT)

Development

PROPOSED TOTAL

BUDGET (MAX.

TWO MILLIONS SR

)

Two millions Saudi Riyals

ESTIMATED

DURATION ( MAX.

24 MONTHS)

24

Months

PROPOSED

STARTING DATE

January 2013 Month / Year

SENIOR PERSONNEL

PROJECT TEAM

No. Name Role Area of

Specialization

1 Dr. Noman Shah P I Organic-Medicinal

Chemistry

2 Dr. Hassan Wadood CO- I Organic-Medicinal

Chemistry

3 Dr. Ahmed CO- I Biochemistry

OTHER PERSONNEL

6 Postdoctoral Associate

7 Ph.D. Student

8 Will be recruited M.S. Student

9 Will be recruited Technician

10 Will be recruited Project Manager

11 Will be recruited Other: Research Assistants

CONSULTANT*

12 Pr. Bill Gates Country: US

13 Pr. Stephon Hawking Country: US

*NOTE: a letter of approval from the consultant/s should be attached with the

application.

KEYWORDS

(MAX. 4)

1. Antidiabetic Type 2 agents 2.

3. 4.

IS THIS PROJECT

BEING SUBMITTED

TO ANY OTHER

FUNDING

INSTITUTION?

No

Yes, please specify

1.

2.

3.



Page 4 of 25

- Summary (English):

Type 2 diabetes is a common chronic disease, characterized by a progressive rise in blood glucose

and worsening insulin resistance that is a major cause of morbidity and mortality. Currently, it is

estimated that more than 16 million people suffering from diabetes live in the Eastern

Mediterranean Region. This staggering figure is expected to extend to almost 43 million by the

year 2025. In case no imperative action is undertaken, the proportion of people living with

diabetes is predicted to jump from 366 million in 2011 to 552 million by 2030, according to new

estimates. This corresponds to almost three new cases every ten seconds or about ten million per

year. Nearly 183 million people are unconscious that they have diabetes according to

International Diabetes Federation (IDF) estimates.

- Summary (Arabic):

رج فو يسوتىي توش تارتفواع تود هوى يوزض يوشي عوا 2ي انىع ( انسكز)يزض إرتفاع انجهىجىس تاندو

أكثوز وتشز انتقودزاخ اانواا انو ا. انسكز ف اندو وتفاقى يقاويح االسىن انذ هى سثة ر س نهزض وانىفاج

يو انتىقو أ وهوذا انوزقى انوذهم. انشوز اووسو فو يففوح يهى عخص عاى ي انسكز عشى 61ي

فو انتىقو أ تقفوش اتخوا أ إجوزا وف اال عدو . 2222عاو ليهى سح تحهى 34يا قزب ي إن زتف

2242تحهوىل عواو يهوى 222اتو 2266 فو يهوى 411يو يوزض انسوكز ي سثح انسكا انذ عشى

حوى عشوزج يالو أو عشوز ثوىا كوم ااالخ إصاتح جددج يا قزب ي ثالث وهذا تىافق ي . جددج وفقا نتقدزاخ

تحا انفودران وفقا نتقدزاخ اال يزض انسكز تأ ندهى يهى سح ال عهى 684 يا قزب يوأ هاك . سىا

.(IDF) اندون نهسكز

1. INTRODUCTION

Diabetes is one of the oldest known diseases. An Egyptian manuscript from 1550 BCE

asserts the sentence “the passing of too much urine” [1]. The great Indian physician

Sushruta (6th century BCE) differentiated the disease and classified it as Medhumeha [2].

The ancient Indians investigated for diabetes by contemplating if ants were tempted by a

person's urine, and designate the ailment "sweet urine disease" (Madhumeha). Presently,

diabetes is the world’s restless propagating chronic disease.

A UN Resolution 61/225 was voted on December 2006 recognizing diabetes as a major

health crisis encountered by all nations of the world. The Resolution baptized 14

November each year as the United Nations World Diabetes. The world Health

Organization recently warned that type II diabetes has become worldly pandemic [3]. In



Page 5 of 25

case no imperative action is taken, the proportion of people living with diabetes is

predicted to increment from 366 million in 2011 to 552 million by 2030, according to

new estimates. This corresponds to almost three new cases every ten seconds or about

ten million per year. Nearly 183 million people are unconscious that they have diabetes

according to International Diabetes Federation (IDF) estimates.

Diabetes mellitus is a chronic metabolic disease that originates when a person has high

blood sugar, either because the pancreatic cells do not produce enough insulin (because

the pancreas does not longer produce or not produce insulin in sufficient amounts), or

when the body cannot respond effectively to the insulin that is produced. Insulin is a

hormone generated by the pancreas that grants the uptake of glucose from the blood by

cells and converts it into energy.

Consequently, glucose present in food and consumed by diabetic people cannot be

converted into energy. Instead of being turned into energy the glucose stays in the blood.

Glucose gets entrapped in the bloodstream and spills into the urine when the muscles and

organs are starved for energy. For this reason blood glucose levels are higher in diabetic

people. The blood’s high sugar content damages the cells of many organs it flows

through. If the levels are very high, they can cause coma or death.

Defection in producing insulin, or of insulin to act properly, or both, generates increased

glucose (sugar) levels in the blood (hyperglycaemia). This is accompanied by long-term

damage to the body and deterioration of various organs and tissues.

Over time, diabetes engenders annihilation or invalidation throughout the body. It

disturbs the blood vessels and the heart, multiplying the risk of heart disease or stroke by

up to four times. Such complications are lethal to two-thirds of people who have diabetes.

By the time they are diagnosed, many people have already deteriorated the blood vessels

in their eyes and 90 percent of them have deterioration after 15 years with the illness; As

a result, almost 40,000 cases of blindness are engendered each year, making diabetes one

of the leading cause of adult-onset blindness [4]. When time passes, the high levels of

sugar in the blood damage the millions of tiny filtering units within each kidney. This

eventually leads to a major complication: kidney failure [5]. Amputations eventuate 10

times more frequently in people with diabetes than in sane people, and the illness also

invalidates the immune system, making people more receptive to serious infection.



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There are three main types of diabetes. First, type 1 diabetes accounts for about 10% of

all diabetes. It results from autoimmune mediated destruction of insulin-secreting β-cells

of the pancreas [6] and solicits daily insulin administration, also referred to as insulin-

dependent diabetes mellitus, IDDM for short, and juvenile diabetes.). Type 1 diabetes

amass alarming chemical substances in their blood from the burning of fat unless

controlled with daily injections of insulin. This can lead to a situation known as

ketoacidosis. This situation is potentially life threatening if not treated. Second, type 2, or

the most common form of diabetes that affects 85-90% of all diabetic people [7]. It is

mainly generated by insulin resistance, a condition in which cells fail to use insulin

properly, formerly referred to as non-insulin-dependent diabetes mellitus, NIDDM for

short, and adult-onset diabetes progressed to require injected insulin. This can develop to

type 1, or latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes) [8].

Type 2 diabetes can remain undetected for many years and the diagnosis is often made

from combined complications or fortuitously through an abnormal blood or urine glucose

analysis. It is often, but not always, in relation with obesity, which itself can cause insulin

resistance and induce elevated blood glucose levels.

Third gestational diabetes (GDM) [9] is another type of diabetes when pregnant women,

who have never had diabetes before, are subjected to high blood glucose levels during

pregnancy which may lead to the development of type 2 DM. It is associated with

complications in the period immediately before and after birth. Other causes of diabetes

include congenital, which is due to genetic defects of insulin secretion, cystic fibrosis-

related, steroid induced by high doses of glucocorticoids, and several forms of

monogenic.

Diabetes without adequate treatments can cause numerous complications. Disastrous

complications comprise diabetic ketoacidosis, or nonketotic hyperosmolar coma. Grave

long-term complications include cardiovascular disease, chronic renal failure, retinal

damage. According to estimations of 2010, there are 285 million people diabetes with

type 2 representing about 90% of the cases. [10]

Other types of diabetes as pre-diabetes illustrate a condition that takes place when a

person's blood glucose levels are more elevated than normal but not high enough for a

diagnosis of type 2 diabetes. Many people destined to develop type 2 diabetes spend

http://www.diabetesaustralia.com.au/en/Understanding-Diabetes/What-is-Diabetes/Ketoacidosis-/



Page 7 of 25

many years in a state of pre-diabetes which has been designated by "largest healthcare

epidemic." [11].

The cause of diabetes relies on the type. Type 1 diabetes is partly inherited and then

triggered by certain infections, with some confirmation implicating Coxsackie B4 virus

[12]. Type 2 diabetes is due primarily to lifestyle factors and genetics [13]. There are

other causes of diabetes [14] including genetic defects of β-cell Function, genetic defects

in insulin processing or insulin action, exocrine pancreatic defects, infections or due to

some drugs.

While there is not yet a cure for diabetes, it can be controlled. The main goal of all

treatment is to control blood sugar levels, but the method varies depending on the type of

diabetes a person has.

The sustained, high plasma glucose levels results in a gradual progression of a number of

complications, including neuropathy, nephropathy, retinopathy, and premature

athereosclerosis [15]. Proper glycemic control is, most likely, necessary for the control of

diabetic complications in type 2 diabetes [16]. However, current therapies to reduce

plasma glucose levels have inherent problems including compliance, ineffectiveness, and

occurrence of hypoglycemic episodes with insulin and sulphonyl urea. Accordingly, there

is a need for more effective, orally administered agents, particularly ones that act as

insulin sensitizing antidiabetic agents in peripheral tissue in order to normalize both

glucose and insulin levels [17].

Therefore, it is crucial to control a convenient blood glucose level especially throughout

the primal phase of the disease [18]. The most commonly utilized oral hypoglycemics for

the disease are sulfonylureas. However these drugs produce severe hypoglycemia and

display primary or secondary failure, which is probably associated with their

particularities as insulin secretagogues [19]. Therefore, the need for nonsulfonylurea class

of hypoglycemic or insulin sensitizers, that does not raise insulin secretion but intensify

the action of insulin is urged [20].



Page 8 of 25

2. PROJECT OBJECTIVES

Three main project objectives are stated below:

1- Design, docking and synthesis of novel diabetic medicine.

2- Pharmacological activity evaluation of the medicine.

3- Search for more potent molecules to be used in clinical development for diabetic

treatment

3. LITERATURE REVIEW

Diabetes mellitus type 2, NIDDM, is a chronic and progressive metabolic disorder of

carbohydrate and lipid metabolism and accounts for the remaining 90 % of diabetes

mellitus [23]. Type 2 diabetes is a metabolic disorder caused, in part, by insulin

resistance in peripheral tissues and/or impaired insulin secretion by the pancreas. In turn,

glucose metabolism is decreased in muscle and thus, fat and glucose output by liver rises.

The resultant high blood glucose level usually generates many dramatic complications

[3]. At the molecular level, the mechanism of insulin resistance in type II diabetes

appears to implicate defects in post-receptor signal transduction [24]. The sustained, high

plasma glucose levels results in a gradual progression of a number of complications,

including neuropathy, nephropathy, retinopathy, and premature athereosclerosis [25].

Therefore, proper glycemic control is, most likely, necessary for the control of diabetic

complications in type 2 diabetes during the early stages of the disease [18, 26]. The

treatment generally prescribed for type 2 diabetes has been a combination of diet,

exercise, and oral hypoglycemic agents such as sulfonylureas and biguanides.

Sulfonylureas, which are insulin secretagogues, stimulate insulin secretion from

pancreatic -cells and are often recognized to generate severe hypoglycemia [27] and

weight gain [28]. In addition, both primary and secondary treatment failure rates with

sulfonylureas are high, causing complications [29]. Therefore, drugs that inverse the

insulin resistance without activating insulin release from cells achieve a major medical



Page 9 of 25

need in the therapy of type II diabetes and hence the potentials to decrease long-term

complications of NIDDM. However, current therapies to reduce plasma glucose levels

have inherent problems including compliance, ineffectiveness, and occurrence of

hypoglycemic episodes with insulin and sulphonyl urea.



Page 10 of 25

1. DESCRIPTION OF THE PROPOSED WORK

4.1 Approach, tasks and phases:

Form RE -D1-2:APPROACH UTILIZED FOR ACHIEVING OBJECTIVES

OBJECTIVE APPROACH OF ACHIEVING THE OBJECTIVE

1

Design, Docking

and Synthesis of

novel medicine

Here, chemistry will be used to accomplish efficiently the synthesis of intermediates and

final products, and the structural identification of compounds through spectroscopic

analysis.

2

Pharmacological

activity evaluation of

the medicine

The second objective will be achieved by providing an in-depth pre-clinical assessment of

the novel medicine.

3

Search for more

potent medicine

The structure-activity relationship will be established for the most potent medicine. This

study will provide insight into the observed diabetic effects and supply evidence for

further development of these compounds for antidiabetic therapy.

Form RE -D1-3: MAPPING OF PHASES AND TASKS TO ACHIEVE OBJECTIVES

OBJECTIVES PHASES TASKS

1

Design, Docking and

Synthesis of novel

medicine

Phase 1: Preparation for launching

the research project

Phase 2: Molecular modelling

docking study)

Phase 3: Synthesis, purification and

characterisation of medicine.

1. Setting-up research lab and purchasing

chemicals, reagents, solvents, glassware, gas

supplies, instruments.

2. Literature review.

1. Construct data base of the 3D structures of

medicine.

2. Molecular modelling fitting studies

between generate common feature.

1. Investigating, developing, performing and

monitoring chemical reactions.

2. Optimization the yield and reaction time

using the microwave irradiation instrument.

3. Training students/technicians

4. Evaluation and discussion of the results

and writing reports.

2

Pharmacological activity

evaluation of the medicine

Phase 4: Preparing materials and

equipment

Acquiring instruments.

1. Tissue culture medicines from insulin

action studies and lipid accumulation.



Page 11 of 25

Phase 5: Assay development and

optimisation

Phase 6: Biological evaluation

2. RNA extraction

1. Evaluation of compound.

2. Evaluation of compounds for their effects

on covalent modification.

3. Evaluation of compounds in cytotoxicity.

4. Evaluation and discussion of the results;

final reporting.

3

Search for more

potent medicine to be used

in clinical development for

diabetic treatment

Phase 7: Preparation of libraries of

medicine for further bio- testing.

1. Acquiring materials.

2. Repeat tasks from objectives 1 and.

3. In vivo evaluation

4. - Writing and submission of a patent

- Writing papers in reputable peer reviewed

journals.

- Participation in conferences to present the

findings

- Write the progress and final report

4.2 Research methodology

Methodology is the systematic, theoretical analysis of the methods applied to a field of study, or

the theoretical analysis of the body of methods and principles associated with a branch of

knowledge. It, typically, encompasses concepts such as paradigm, theoretical model, phases and

quantitative or qualitative techniques.[1]

A Methodology does not set out to provide solutions but offers the theoretical underpinning for

understanding which method, set of methods or so called “best practices” can be applied to a

specific case.



Page 12 of 25

It has been defined also as follows:

1."the analysis of the principles of methods, rules, and postulates employed by a discipline";[2]

2."the systematic study of methods that are, can be, or have been applied within a discipline";[2]

3."the study or description of methods".[3]

In recent years, the word methodology has become a "pretentious substitute for the word method".[4]

Many recent uses of the word methodology mistakenly treat it a synonym for method or body of methods.

Doing this shifts it away from its true epistemological meaning and reduces it to being the procedure

itself, the set of tools or the instruments that should have been its outcome. A methodology is the design

process for carrying out research or the development of a procedure and is not in itself an instrument for

doing those things. Using it as a synonym for method or set of methods, leads to misinterpretation and

undermines the proper analysis that should go into designing research. Generally for any research study

both primary and secondary research are done which facilitates in the better understanding of the entire

study. Primary research helps garner relevant and adequate data of the current state of affairs pertaining to

any subject and provides an insight into the exact nature of the problem. Owing to the broad and complex

nature of this research topic which would require delving into many aspects of the study including an

ethnographic study which would in turn include a longitudinal time horizon which cannot be possibly

encompassed within this research as it goes well beyond the possibilities of an academic research.The use

of pre-packaged, 'ready-to-go' methods do not constitute a methodology and are no substitute for the

necessary scientific search for the most appropriate method to approach a problem".[

4.3 Management Plan

The Form RE -D1-4: ROLE AND INVOLVEMENT DURATION OF PROJECT TEAM

TEAM MEMBERS ROLE DURATION

(MONTHS)

SENIOR PERSONNEL:

Dr. Noman Shah -Supervising and managing the project.

-Coordination of the progress work between the two sites

-Responsible for administrative, reporting and purchasing

requirements.

-Conducting all experiments to test the feasibility.

-Optimizing yield and reaction time with microwave instrument.

-Training staff in synthesis, purification, spectroscopic analysis

and microwave instrument.

-Following-up the practical work of staff

-Interpretation of results

-Communicate findings through reports, publications and

presentation in international congress.

24

Dr. Hassan Wadood -Designing, docking and performing medicine.

-Conducting all experiments to test the feasibility of the

approach.

20



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-Optimizing yield and reaction time with microwave instrument.

-Training staff in synthesis, purification, spectroscopic analysis

and microwave instrument.

-Following-up the practical work of staff

-Interpretation of results.

-Writing reports to PI.

-Contribution in writing and submitting paper for publication

Dr. Ahmed -Setting up of the cell culture laboratory

-Acquiring materials for cell culture, RNA analysis, insulin

action and bioassays.

--Analysing and reporting of results.

-Training students and staff in bio-testing.

-Writing of reports,

-Contribution in writing and submitting paper for publication.

20

OTHER PERSONNEL:

Project Manager - Conducting quotations, purchasing, following up materials

-Performing and following up all administrative work

-Budgeting

- Ticketing

20

Research Assistant

M.S. Student

Technicians

-Conducting chemical reactions, purification

-Performing the technical task in the lab, operation instruments

and characterization of products

-Conducting biological assays

-Reporting and evaluating results

-Writing first draft report

20

7

14

CONSULTANT:

Pr. Bill Gates Providing technical assistance for conducting bio-tests

2

Pr. Stephen Hawking Providing technical assistance for molecular modelling

2



Page 14 of 25



Page 15 of 25

FormRE- D1-5: WORK PLAN AND TIME SCHEDUAL

24 23 22 21 20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 INVOLVEMENT

DURATION PHASES & TASKS

Participation PHASE I

x x NS Task 1.1: Setting-up research lab and

purchasing chemicals, reagents,

solvents, glassware, gas supplies,

instruments.

x x x x x x x NS, HW Task 1.2: Literature review

PHASE 2

x x x x x x x NS, HW Task 2.1: Construct data

PHASE 3

x x x x x x x x x x x x x x x x x x x NS, HW Task 3.1: Investigating, developing,

performing and monitoring chemical

reactions.

x x x x x x x x x x x x x x x x NS, HW Task 3.2: Optimization the yield and

reaction time using the microwave

irradiation instrument.

x x x x x x x x x x x x x x x x x x x NS, HW Task 3.3: Employing crystallisation,

distillation and separation

chromatographic techniques.

x x x NS, HW, AM Task 3.5: Training

students/technicians

x x x Task 3.6: Evaluation and discussion

of the results and writing reports

PHASE 4

Noman Shah (NS), Hassan Wadood (HW), Ahmad (AM)



Page 16 of 25

4.4 Project Deliverables:

FormRE- D1-6: RELATIONSHIP TO STRATEGIC FRAMEWORK2

PROJECT

EXPECTED

OUTCOMES

STRATEGIC TECHNOLOGY PROGRAM GOALS PROJECT

OBJECTIVES

ACHIEVED GOAL 1 GOAL 2 GOAL3

Development of

novel

MEDICINE

Develop

undergraduate and

vocation training

programs and on-the-

job training

opportunities to create

a pool of technically

skilled support staff

and technicians who

are committed to good

laboratories practices

Increase national

scientific discovery

and productivity

through

dissemination of

findings via

publications in peer-

reviewed and

reputed journals

1

Design docking and

synthesis of novel

medicine

Identification of

leads as

potential potent

medicine

Develop postgraduate

training to create a

locally competent

talent capable of

conducting novel

medical and health

sciences research

Develop

mechanism for

private fund-

raising for

research through

industry

partnerships

Establishing national

mechanisms for

capturing intellectual

properties and

accelerating their

commercialization

2

Pharmacological

activity evaluation

of the medicine

Identify

potential drug

candidates for

diabetic therapy

Prepare competitive

recruitment package

in order to attract,

retain and nurture

first-class researchers

Establish

infrastructure to

facilitate and

expedite

acquisition of

resources

Develop mechanism

to encourage

research

partnerships and

create new industries

&

Promote

performance of basic

and translational

interdisciplinary

research for better

understanding and

treatment of diseases

pertinent to the KSA

3

Search for more

potent medicine



Page 17 of 25

The three expected outcomes of this research project allow the achievement of many goals of the

Strategic Technology Program Goals (Strategic Priorities for Medical and Health program in Saudi

Arabia) described in the form RE-D-1-6. In this section we develop the relationships of the

outcomes of the project to the objectives and the linkages with the related goals.

OUTCOME 1 (Development of novel medicine)) will be the achievement outcome of the first

objective Design, docking and synthesis of novel medicine

GOAL 1: Develop undergraduate and vocation training programs and on-the-job training

opportunities to create a pool of technically skilled support staff and technicians who are

committed to good laboratories practices

GOAL 3: Increase national scientific discovery and productivity through dissemination of

findings via publications in peer-reviewed and reputed journals

OUTCOME 2 (Identification of leads as potential potent medicine) will be the achievement of the

second objective: Pharmacological activity evaluation of the medicine systems.

GOAL 1: Develop postgraduate training to create a locally competent talent capable of

conducting novel medical and health sciences research

GOAL 2: Develop mechanism for private fund-raising for research through industry

partnerships

GOAL 3: Establishing national mechanisms for capturing intellectual properties and

accelerating their commercialization

OUTCOME 3 (Identify potential drug candidates for diabetic therapy) will be the achievement of

the third objective: Search for more potent molecules to be used in clinical development for

diabetic treatment.

GOAL 1: Prepare competitive recruitment package in order to attract, retain and nurture

first-class researchers

GOAL 2: Establish infrastructure to facilitate and expedite acquisition of resources

GOAL 3: Develop mechanism to encourage research partnerships and create new industries

&: Promote performance of basic and translational interdisciplinary research for better

understanding and treatment of diseases pertinent to the KSA



Page 18 of 25

5. VALUE TO THE KINGDOM

This research project will be conducted in the field of medicinal chemistry, at the cutting edge of

diabetes research. The focus on development of new synthetic drug compounds ended up in

amalgamating many other disciplines such as biochemistry, pharmacology, molecular biology and

medicine into medicinal chemistry.

Umm Al-Qura University, ranked as one of the foremost biotechnology universities in KSA, is

committed to providing an exceptional platform in which both researchers and students can excel,

and achieve their professional and personal goals.

Accordingly, this research project creates foundations for university-based research and its valuable

beneficial impact on different levels namely: academia, industry society and economy in KSA.

At the academic level, the project will:

- provide a multidisciplinary environment that encourages creativity and scientific investment in the

field of pharmaceutical technology; working in teams is essential for drug discovery because many

different aspects of a molecule (preparation, isolation, characterization, biological and

pharmacological studies..) must be identified for a clinical studies candidate.

- exploit the research capacity in the Faculty of Pharmacy and the Faculty of Medicine at Umm Al-

Qura university for the aim of creating novel knowledge which can be exploited by supporting

continuous educational improvement and implementation of new undergraduate and graduate

(Master, Ph.D.) curricula.

- encourage inter-universities interactions (King Saud University KSA, Newcastle University UK) to

generate constructive alliances and synergy between local and/or international researchers and to

build affiliations and partnerships with renowned international universities.

- offer pharmaceutical industry focused programs as specialized programs to form graduates for

career focus tracks in real-world pharmaceutical industry.

- train Saudi students to master a wide range of synthetic methods, analytical techniques, medicinal

chemistry skills and biological testing methods. Students are placed in a competitive position as they

are developed, for a challenging and rewarding professional career in chemical and pharmaceutical

research to design, synthesize and identify chemical leads for drug discovery.

- facilitate placements of Saudi graduates in pharmaceutical and chemical industry sectors as well as

laboratories, research centers, universities and institutes of technology since they may be involved in

pharmaceutical research, biological/therapeutic evaluation of medicinal products and

production/manufacture, quality control, quality assurance and process development.

- offer short courses, workshops, and support seminars for undergraduates and graduates students.



Page 19 of 25

- generate conferences which can provide a forum for local and international researchers, students,

entrepreneurs and industry leaders to deliberate innovation in diabetes therapy.

- use the current research center which embodies a highly integrated basic and translational

multidisciplinary environment for better understanding and annihilating of diseases pertinent to the

KSA. The key to success is converting the latest scientific achievements generated by research into

innovative therapeutic treatments able to significantly improve the cure rates for cancer with

simultaneous elimination of side effects. The center will extend the spectrum of research interests to

cover other areas focused on development of cardiovascular, anticancer and other therapies, with a

particular emphasis on understanding the individual's quality of life of the Saudi society.

At the industrial, social and economic levels, the interest of developing new local anitdiabetic agents

will:

- achieve the effective transfer and implementation of research results and technology to medical local

institutions in the private and public sectors in KSA and raises their ability to take advantage of the

scientific knowledge generated by academia.

- bridge the gap between cutting edge academic research and industrial development of diabetes

therapeutics and diagnostics.

- maximize diabetic patient cost-benefit from publicly funded research in an attempt to tackle

concerns about care costs.

- ensure the foundations of a modern economy and a modern society in KSA which rely on advanced

technology.

- deliver better health incomes to diabetic patients by ameliorating their quality and length of life.

- improve the access to higher clinical therapeutic quality for Saudi diabetic patients concomitant with

the decrease of the costs and deficits of the national health insurance of KSA in the care of patients

with chronic diseases.

Consequently, this project could pave the way for advancements and betterments in many strategic

sectors of the Kingdom.



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6. PROJECT EXECUTION

In preamble, we found it necessary to introduce the main researchers of the multi-disciplinary group

and the consultancy team who will be involved in the proper execution of this research project.

6.1 Current Resources:

This research proposal has not been submitted to any other sources of funding.

The physical location of the research at the Faculty of Pharmacy is in dedicated areas for drug discovery and

development specifically designated for that purpose. The research center, approx. 80 square meters, is

located in the basement of the building of the faculty. It is a modern facility providing all infrastructures

essential for general lab operation, including vacuum, compressed gas. The space accommodates 4 fume

hoods and 10 benches.

The equipments available at Umm Al-Qura University in the Faculty of Pharmacy that will be helpful for

the realization of the project are:

1- Infra-Red Spectroscopy (Nicolet 200 from Thermo Company) which will be used for examining the

functional group present or absent in the compound.

2- Discovery Studio 3.1 software which will be used to perform molecular modeling of compounds

The equipment’s available at Umm Al-Qura University in the Faculty of Medicine that will be helpful for

the realization of the project are:

1- Safety cabinet and CO2 incubator will be used for tissue culture of tumor cell lines.

2- UV-Visible spectroscopy from Thermo which will be used for studying the DNA binding and for

determining the growth inhibition concentration of molecules using MTT assay.

The science library at the Umm Al-Qura University provides an extensive range of chemistry and biology

reference texts and major journals. The library also subscribes to a data base in chemistry (Sci-Finder) and to

the online journals database Science Direct and ACS which provide access to a worldwide range of

scientific research publications.

6.2 Requested Resources:

1] Human resources:



Page 21 of 25

The proposed project will be conducted in two sites of Umm Al-Qura University (Mecca): College of

Pharmacy and College of Medicine.

The research team involved in this project will consist of researchers with different fields of expertise: two

medicinal chemists and a biochemist (see in preamble of this section).

Two research assistants (part-time), one MS student and two technicians will be hired for the project. Many

undergraduate students enrolled in pharmacy and chemistry curriculum will have the opportunity to be

engaged in this research project at the chemistry-biology interface. They will perform the experiments,

measurements, biological tests, and result analyses.

A project manager will be recruited to facilitate the administrative work for the realization of the project.

2] Equipments, materials and consumables:

Taking into account the nature and complexity of the research proposal, the following resources are

necessary for the proper execution of the project:

Year 1 Year 2 Supplies:

Chemicals, Reagents for synthetic chemistry 60000 30000

Solvents, Chromatography supplies,

NMR consumables and amalysis

60000 60000

Elemental analysis for C, H and N 40000 40000

consumables 20000 20000

Service and maintenance of NMR, GC/MS 20000 30000

Tissue culture supplies 100000 20000

Chemicals, reagents, supplies for cell-free experiments 50000 30000

Mice 80000

consumables 30000 30000

Supplies Total: 460000 260000

Instrument

CEM Discover focused microwave synthesis instrument 210000

water bath, rotavapor 65000

Total Direct Costs: 735000 260000

SEE INSTRUCTIONS

BEFORE COMPLETING FORM RE- D1-7: PROPOSED BUDGET (in Saudi Riyals)

PROJECT TITLE: COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN, SYNTHESIS AND

ANTIDIABETIC EVALUATION OF CERTAIN NEW THIAZOLIDINEDIONE (TZD)

ANALOGUES FOR DEVELOPING NEW POTENTIAL ANTIDIABETIC TYPE 2

AGENTS

DURATION: (24) MONTHS

ITEM: CATEGORY NO. COMPENSATION FIRST YEAR SECOND YEAR

TOTAL Months Budget Months Budget

Man

po

wer

Consultants 2 10000 2 40000 2 40000 80000

Principal investigator 1 6000 12 72000 12 72000 144000

Co-investigator 2 5000 10 100000 10 100000 200000



Page 22 of 25

Co-investigator

Research assistants

(MS holder)

2 5000 10 100000 10 100000 200000

PhD students

Ms students 1 6000 7 42000 42000

Undergrads students

Project manager 1 3000 10 30000 10 30000 60000

Technicians 2 2000 7 28000 7 28000 56000

Secretarial- clerical

Other

Su

mm

er

com

pen

s. Compensation 1

Compensation 2

Total (including summer compensation) 370000 412000 782000

Equ

ipm

ent

&

mat

eria

ls

major equipment ( <= 100.000) 210000 210000 Equipment (> 100,000) 65000 65000 Materials & supplies 460000 260000 720000

Item total 735000 260000 995000

Tra

vel

Conferences 10000 10000 Training Field trips Tickets 15000 15000 30000

Item total 15000 25000 40000

Oth

ers

Patent registration 15000 15000 Publications 10000 10000 Workshop Other expenses 8000 10000 18000

Item total 8000 35000 43000

7% for SCIENCE AND TECHNOLOGY UNIT 84903 55097 140000

Grand total 1212903 787097 2000000

Compensations (including summer compensation) 39.1% 782000

Equipment& materials 49.75% 995000

Travel 2.0% 40000

Others 2.15% 43000

SCIENCE AND TECHNOLOGY UNIT 7 % 140000

Grand total 100% 2000000

6.4 Budget Justification:

The proposal entitled “COMPUTRER BASED MOLECULAR MODELING, DRUG DESIGN,

SYNTHESIS AND ANTIDIABETIC EVALUATION OF MEDICINE” promises for the Kingdom

of Saudi Arabia to achieve all the objectives mentioned in section 2.

Consultant:

Bill Gates will be approached regarding the biological activity of medicine.



Page 23 of 25

Their respectively field of expertise will be highly valued for the execution of the project.

The participation of research assistants (MS holder, part-time), graduate (MS student),

technicians as well as undergraduate students is essential for the execution of the project. They

will acquire a variety of techniques and skills from the synthesis to the biological testing. The

research team will dedicate maximum time to achieve the goals of this proposal

The remuneration of man power is set at 39.1% of the total proposed budget. 49.75% of the total

budget is devoted to cover expenses in equipment and material for the proper execution of the

project. 2% of the funds will be utilized to enhance knowledge in terms of attending conferences

and symposiums in order to execute the project in successfully. 2.15% will be used for patent

registration, publications and preparation of the project reports. Finally, 7% of the budget will

cover the administrative work of the Science and Technology Unit.

Budget justification for acquiring the following instrument:

CEM Discovery microwave irradiation instrument will be purchased using the requested funds.

The acquisition of this instrument will be beneficial for research activities. It has found many

applications in chemical synthesis particularly in the pharmaceutical industry for developing

compounds in the lead optimization phase of drug development. The acquisition of such an

instrument will enhance the research potential of faculty members, and provide the solid and

necessary support for the medicinal chemistry curriculum. The involvement in research activities

is necessary for providing training projects to undergraduate and graduate students in the faculty

of pharmacy of Umm Al-Qura University in the field of medicinal chemistry.



Page 24 of 25

8. UNDERTAKING OF THE PROJECT TEAM

Form RE- D1-8: UNDERTAKING OF THE PROJECT TEAM

The project team undertakes that this project or any part of it, is:

1- Prepared in full conformity with the SCIENTIFIC INTEGRITY RULES.

2- Original work of the signatories or individuals working under their supervision, including the text, graphics,

publications, and documents, unless otherwise indicated.

3- Not funded by any other sources.

4- Not submitted to any other funding institution during the evaluation process.

5- Not sought fund from any other sources if it is funded by the NSTIP.

SIGNATURE ID NUMBER3 NAME ROLE

2321234567

Dr. Noman Shah PI

2321234568

Dr. Hassan Wadood

COI. 1

2321234569

Dr. Ahmad

COI. 2

3ID number includes National ID for citizens and Iqama for non-citizens team members.



Page 25 of 25

9. REFERENCES:

^ Irny, S.I. and Rose, A.A. (2005) “Designing a Strategic Information Systems Planning Methodology

for Malaysian Institutes of Higher Learning (isp- ipta), Issues in Information System, Volume VI, No. 1,

2005.

2.^ Jump up to: a b Methodology Usage Notes, entry at Merriam–Webster

3.Jump up ^ Baskerville, R. (2009). 35. "Computer and Information Security Handbook aha". Computers

& Security. Morgan Kaufmann Publications (ᾘ ed.) (Elsevier Inc) 10 (8): 605 Extra |pages= or |at=

(help). ISBN 978-0-12-374354-1

4.^ Jump up to: a b misuse of the word Methodology in technical contexts

5.Jump up ^ See, for example, Thomas Kuhn, The Structure of Scientific Revolutions (University of

Chicago, 1970, 2nd ed.)

10. RESUMES:

Health & Medicine

Application form Research Project Proposal