CHAPTER IVCHAPTER IVCHAPTER IVCHAPTER IV

Result & DiscussionResult & DiscussionResult & DiscussionResult & Discussion

overall conclusionoverall conclusionoverall conclusionoverall conclusion

4.1 Result and discussion

The heterocyclic skeleton containing nitrogen atom is the basis of many

essential pharmaceuticals and of many physiologically active natural products. 2-

Pyridone is nitrogen containing synthetically designed scaffold with a broad spectrum

of biological activities. Its derivatives have been claimed to be non-nucleoside HIV

Type I specific reserve transcriptase inhibitors, anti-inflammatory activities, a

valuable building block in the construction of piperidines, perhydroquinolones,

indolzidines, quinolizidines, alkaloid ring systems and have wide range of biological

and pharmacological activities. The 2-pyridone moiety, frequently found in a variety

of interesting compounds has received remarkable attention due to its promising

features as a key scaffold and in privileged building blocks. A wide range of

biological activities have been observed in compounds possessing a 2-pyridone which

includes antitumor, antifungal, antibacterial, anti-inflammatory, antiviral and

antithrombotic properties.

In our previous work, we have synthesized 2-pyridones by incorporating

various substituted secondary heterocyclic amines at C-6 position and studied their

antimicrobial activities and in continuation of this work we have synthesized several

new derivatives of 2-pyridones by incorporating the various amines i.e. triazole and

pyrrolidine at C-6 position of 2-pyridones. Our purpose of present work was to

observe, the variation in antimicrobial properties after structural changes and SAR

studies.

The Minimum Inhibitory Concentrations (MICs) of the synthesized

compounds were carried out by broth microdilution method. Antibacterial activity

was screened against two Gram negative bacteria (E. coli MTCC 442, P. aeruginosa

MTCC 2488) and two Gram positive bacteria (S. aureus MTCC 96, S. pyogenes

MTCC 443). Gentamycin, norfloxacin, ciprofloxacin, chloramphenicol and ampicillin

were used as standard antibacterial drugs. Antifungal activity was screened against

three fungal species C. albicans MTCC 227, A. niger MTCC 282 and A. clavatus

MTCC 1323. Nystatin and greseofulvin were used as standard antifungal drugs. The

results of antibacterial and antifungal activities of each species have been compared

with standard drugs (already discussed in Chapter II and Chapter-III). From

microbial screening results we have selected several compounds to screen against

Mycobacterium tuberculosis H37Rv and compared with standard drug rifampicin and

isoniazid. The results are represented in graphical manner and summarized as follows;

4.1.1 Antibacterial studies

Antibacterial activity of Chapter-II (methoxy derivatives)

Minimum Inhibitory Concentrations against E. coli

From the antibacterial results of intermediate 1-5, compound 1 and 4 showed

good activity at 100 µg/ml compared to ampicillin.

In series 1, compounds 6 and 17 showed very good activity at 62.5 µg/ml;

whereas 7 and 13 possessed good activity at 100 µg/ml compared to ampicillin.

In series 2, compound 24 and 32 showed good activity at 100 µg/ml

compared to ampicillin. Compound 36 showed good activiy at 100 µg/ml compared to

ampicillin.

Fig. 1: Minimum Inhibitory Concentrations of 1-37 against E. coli

From series 3, compound 38 exhibited very good activity at 62.5 µg/ml;

whereas 39 and 50 possessed good activity at 100 µg/ml with ampicillin.

In series 4, compound 64 showed very good activity at 62.5 µg/ml; whereas 56

and 63 possessed good activity at 100 µg/ml. compound 68 also showed good activiy

at 100 µg/ml compared to ampicillin.

Fig. 2: Minimum Inhibitory Concentrations of 38-69 against E. coli

Compounds of Chapter-II exhibited promising activities against E. coli are listed

below;

CH3O

COOH

COOH

CH3O N

O Cl

N N

N

CH3O

N

N

N

O Cl

N N

N

1 (MIC = 100 µg/ml) 4 (MIC = 100 µg/ml) 6 (MIC = 62.5 µg/ml)

CH3O

N

N

N

O Cl

N N

N

ClCl

CH3O

N

N

N

O Cl

N

CH3O N

O Cl

NN

N

Cl

Cl

17 (MIC = 62.5 µg/ml) 38 (MIC = 62.5 µg/ml) 64 (MIC =62.5 µg/ml)

CH3O

N

N

N

O Cl

R

N N

N

CH3O

N

N

N

O Cl

N N

N

R

CH3O

N

N

N

O Cl

R

N

6, 7 and 13 (MIC = 100 µg/ml) 24 and 32 (MIC = 100 µg/ml) 39 and 50 (MIC = 100 µg/ml)

Where R= H; 2-Cl; 2-NO2 Where R= 4-Cl; 3, 4-Cl Where R= 2-Cl; 2-Cl, 4-NO2

CH3O

N

N

N

O Cl

N

R

CH3O N

O Cl

N

N

NN

56 and 63 (MIC = 100 µg/ml) 68 (MIC = 100 µg/ml)

Where R= 4-Cl; 2, 5-Cl

Minimum Inhibitory Concentrations against P. aeruginosa

From the antibacterial results of intermediate 1-5, compound 4 showed good

activity at 100 µg/ml compared to ampicillin.

In series 1, compounds 6 and 7 possessed good activity at 100 µg/ml. From

series 2, compounds 22 exhibited good activity at 100 µg/ml compared to ampicillin.

Compounds 36 also possessed good activity at 100 µg/ml compared to ampicillin.

Fig. 3: Minimum Inhibitory Concentrations of 1-37 against P. aeruginosa

From series 3, compounds 46 and 50 exhibited good activity at 100 µg/ml. In

series 4, compounds 54 and 65 possessed good activity at 100 µg/ml. Compounds 68

possessed good activity at 100 µg/ml compared to ampicillin.

Fig. 4: Minimum Inhibitory Concentrations of 38-69 against P. aeruginosa

Compounds of Chapter-II exhibited promising activities against P. aeruginosa

are listed below;

CH3O N

O Cl

N N

N

CH3O

N

N

N

O Cl

N N

N

CH3O

N

N

N

O Cl

N N

N

Cl

4 (MIC = 100 µg/ml) 6 (MIC = 100 µg/ml) 7 (MIC = 100 µg/ml)

CH3O N

O Cl

N N

N

N

NCl

CH3O N

O Cl

N

N N

N

N

N

CH3O

N

N

N

O Cl

N

NO 2

22 (MIC = 100 µg/ml) 36 (MIC = 100 µg/ml) 46 (MIC = 100 µg/ml)

H3CO

N

N

N

O Cl

N

Cl

O2N

CH3O N

O Cl

NN

NCl

CH3O N

O Cl

NN

NCl

O2N

50 (MIC = 100 µg/ml) 54 (MIC = 100 µg/ml) 65 (MIC = 100 µg/ml)

CH3O N

O Cl

N

N

N

N

68 (MIC = 100 µg/ml)

Minimum Inhibitory Concentrations against S. aureus

In series 1, compound 8 and 13 showed very good activity at 100 µg/ml

compared to ampicillin; others showed moderate to good activity. In series 2,

compound 23, 26 and 28 possessed very good activity at 100-150 µg/ml; whereas

compounds 24, 25 and 31 possessed poor activity. All other compounds showed good

activity. Compound 36 showed good activity when compared to ampicillin.

Fig. 5: Minimum Inhibitory Concentrations of 1-37 against S. aureus

In series 3, compounds 40, 45 and 47 showed very good activity at 100 µg/ml,

where as compounds 39, 42 and 48 showed poor activity. Rest of the compounds

exhibited good activity. In series 4, compounds 55 and 60 possessed very good

activity at 100 µg/ml; where as the remaining compounds showed good activity

except compounds 56, 57 and 63 which displayed poor activity

Fig. 6: Minimum Inhibitory Concentrations of 38-69 against S. aureus

Compounds of Chapter-II exhibited promising activities against S. aureus are

listed below;

CH3O N

O

Cl

Cl

CH3O

N

N

N

O Cl

N N

N

Cl

CH3O

N

N

N

O Cl

N N

N

NO2

3 (MIC = 100 µg/ml) 8 (MIC = 100 µg/ml) 13 (MIC = 62.5 µg/ml)

CH3O N

O Cl

N N

N

N

N

Cl

CH3O N

O Cl

N N

N

N

NO2N

CH3O

N

N

N

O Cl

N

Cl

23 (MIC = 100 µg/ml) 28 (MIC = 100 µg/ml) 40 (MIC = 62.5 µg/ml)

CH3O

N

N

N

O Cl

N

NO2

CH3O

N

N

N

O Cl

N

O2N

CH3O N

O Cl

NN

N

Cl

45 (MIC = 100 µg/ml) 47 (MIC = 100 µg/ml) 55 (MIC = 100 µg/ml)

CH3O N

O Cl

NN

NO2N

60 (MIC = 100 µg/ml)

Minimum Inhibitory Concentrations against S. pyogenes

Intermediate compound 3 exhibited good activity. In series 1, compounds 8

and 13 showed good activity at 100 µg/ml. In series 2, compounds 23 and 28

possessed good activity at 100 µg/ml with ampicillin.

Fig. 7: Minimum Inhibitory Concentrations of 1-37 against S. pyogenes

In series 3, compounds 40, 45 and 48 showed good activity at 100 µg/ml. In

series 4, compounds 55 and 63 possessed good activity at 100 µg/ml with ampicilin.

Fig. 8: Minimum Inhibitory Concentrations of 38-69 against S. pyogenes

Compounds of Chapter-II exhibited promising activities against S. pyogenes are

listed below;

CH3O N

O

Cl

Cl

CH3O

N

N

N

O Cl

N N

N

Cl

CH3O

N

N

N

O Cl

N N

N

NO2

3 (MIC = 100 µg/ml) 8 (MIC = 100 µg/ml) 13 (MIC = 100 µg/ml)

CH3O N

O Cl

N N

N

N

N

Cl

CH3O N

O Cl

N N

N

N

NO2N

CH3O

N

N

N

O Cl

N

Cl

23 (MIC = 100 µg/ml) 28 (MIC = 100 µg/ml) 40 (MIC = 100 µg/ml)

CH3O

N

N

N

O Cl

N

NO2

CH3O

N

N

N

O Cl

N

ClCl

CH3O N

O Cl

NN

N

Cl

45 (MIC = 100 µg/ml) 48 (MIC = 100 µg/ml) 55 (MIC = 100 µg/ml)

CH3O N

O Cl

NN

NCl

Cl

63 (MIC = 100 µg/ml)

Antibacterial activity of Chapter-III (Ethoxy derivatives)

Minimum Inhibitory Concentrations against E. coli

From the antibacterial results of intermediate 101-106, compound 105 showed

good activity at 100 µg/ml compared to ampicillin.

In series 1, compound 108 showed very good activity at 62.5 µg/ml; whereas

compounds 107, 117 and 119 possessed good activity at 100 µg/ml compared to

ampicillin.

In series 2, compound 123 showed very good activiy compared to ampicillin

whereas compounds 122, 124, 127, 130 and 133 possessed good activity at 100

µg/ml.Compound 136 also showed good activity when compared to ampicillin.

Fig. 9: Minimum Inhibitory Concentrations of 101-137 against E. coli

In series 3, compounds 140, 144 and 149 showed good activity at 100 µg/ml

compared to ampicillin.

In series 4, compound 156 showed very good activiy at 50 µg/ml compared to

ampicillin; whereas compounds 154, 162 and 166 showed good activity at 100 µg/ml.

Fig. 10: Minimum Inhibitory Concentrations of 138-169 against E. coli

Compounds of Chapter-III exhibited promising activities against E. coli are

listed below;

C2H5O N

O Cl

N

C2H5O

N

N

N

O Cl

N N

N

Cl

C2H5O N

O Cl

N N

N

N

N

Cl

105 (MIC = 100 µg/ml) 108 (MIC = 62.5 µg/ml) 123 (MIC = 62.5µg/ml)

C2H5O N

O Cl

N N

N

N

NN

C2H5O N

O Cl

NN

N

Cl

C2H5O

N

N

N

O Cl

R

N N

N

136 (MIC = 62.5µg/ml) 156 (MIC = 62.5µg/ml) 107, 117 and 119 (MIC = 100 µg/ml)

Where R= 2-Cl; 3, 4-Cl; 4-Cl, 2-NO2

C2H5O

N

N

N

O Cl

N N

N

R

C2H5O

N

N

N

O Cl

R

N

122, 124, 127, 130 and 133 (MIC = 100 µg/ml) 140, 144 and 149 (MIC = 100 µg/ml)

Where R=2-Cl; 4-Cl; 4-CH3; 4-NO2; 2-Cl, 4-NO2 Where R= 3-Cl; 4-CH3; 2, 5-Cl

C2H5O

N

N

N

O Cl

N

R

154, 162 and 166 (MIC = 100 µg/ml)

Where R= 2-Cl; 4-NO2 ; 4-Cl, 2-NO2

Minimum Inhibitory Concentrations against P. aeruginosa

In series 1, compounds 114 and 120 showed good activity at 100 µg/ml. In

series 2, compound 121 and 135 possessed good activity at 100 µg/ml compared to

ampicillin.Compound 137 also showed good activity at 100 µg/ml when compared to

ampicillin.

Fig. 11: Minimum Inhibitory Concentrations of 101-137 against P. aeruginosa

In series 3, compounds 141 and 146 showed good activity at 100 µg/ml. In

series 4, compound 163 and 167 possessed good activity at 100 µg/ml with ampicillin.

Fig. 12: Minimum Inhibitory Concentrations of 138-169 against P. aeruginosa

Compounds of Chapter-III exhibited promising activities against P. aeruginosa

are listed below;

C2H5O

N

N

N

O Cl

N N

N

NO2

C2H5O

N

N

N

O Cl

N N

N

Cl

O2N

Cl

C2H5O N

O Cl

N N

N

N

N

114 (MIC = 100 µg/ml) 120 (MIC = 100 µg/ml) 121 (MIC = 100 µg/ml)

C2H5O N

O Cl

N N

N

N

N

O2N

Cl

Cl

C2H5O N

O Cl

N

N N

N

C2H5O

N

N

N

O Cl

N

Cl

135 (MIC = 100 µg/ml) 137 (MIC = 100 µg/ml) 141 (MIC = 100 µg/ml)

C2H5O

N

N

N

O Cl

N

NO2

C2H5O N

O Cl

NN

NCl

Cl

C2H5O N

O Cl

NN

N

O2N

Cl

Cl

146 (MIC = 100 µg/ml) 163 (MIC = 100 µg/ml) 167 (MIC = 100 µg/ml)

Minimum Inhibitory Concentrations against S. aureus

From the antibacterial results of intermediate 101-105, compound 101 showed

good activity at 25 µg/ml when compared with chloromphenicol and ciprofloxacin

while others inhibited good activity at 250 µg/ml compared to ampicillin.

In series 1, compounds 108, 115 and 119 showed very good activity at 100-

150 µg/ml; compounds 112, 114, 111, 113, 117 and 120 showed good activity at 200-

250 µg/ml with ampicillin.

In series 2, compounds 130 and 134 showed very good activity at 100-125

µg/ml; compounds 127, 129, 123, 127, 129 and 132 showed good activity at 200-250

µg/ml; while others showed moderate to weak activity between 250-500 µg/ml with

ampicillin. Compound 136 showed good activity at 250 µg/ml.

Fig. 13: Minimum Inhibitory Concentrations of 101-137 against S. aureus

In series 3, compounds 140, 141 and 149 exhibited very good activity at 100-

150 µg/ml; Compounds 145, 146, 143, 144, 151 and 152 exhibited good activity at

200-250 µg/ml with ampicillin. In series 4, compound 166 showed very good activity

at 100 µg/ml, ; Compounds 158, 159, 161, 165 and 168 exhibited good activity at

150-200 µg/ml at with ampicillin.Compound 167 showed good activity at 200 µg/ml

with ampicillin.

Fig. 14: Minimum Inhibitory Concentrations of 138-169 against S. aureus

Compounds of Chapter-II exhibited promising activities against S. aureus are

listed below;

C2H5O

COOH

COOH

C2H5O

N

N

N

O Cl

N N

N

Cl

NO2

C2H5O N

O Cl

N N

N

N

N

Cl

O2N

1 (MIC = 25 µg/ml) 119 (MIC = 100 µg/ml) 134 (MIC = 100 µg/ml)

C2H5O

N

N

N

O Cl

N

ClCl

C2H5O N

O Cl

NN

N

Cl

O2N

149 (MIC = 50 µg/ml) 166 (MIC = 100 µg/ml)

Minimum Inhibitory Concentrations against S. pyogenes

From the results of intermediate 101-106, compound 101 showed good

activity at 12.5 µg/ml with norfloxacin whereas compound 105 showed good activity

at 100 µg/ml with ampicillin

In series 1, compound 119 and 120 showed good activity at 100-125 µg/ml

compared to with ampicillin; whereas 108 and 114 showed moderate activity at 200

µg/ml.

In series 2, compound 134 and 135 showed good activity at 100-125 µg/ml;

whereas 123, 129 and 133 showed moderate activity at 200 µg/ml.

Fig. 15: Minimum Inhibitory Concentrations of 101-137 against S. pyogenes

In series 3, compound 141 showed good activity at 62.5 µg/ml compared to

chloramphenicol and ciprofloxacin; whereas 149 and 151 showed good activity at

100-125 µg/ml with ampicillin.

In series 4, compounds 164, 166 and 167 showed good activity at 100-125

µg/ml with ampicillin. Rest of compounds displayed moderate to week activity.

Fig. 16: Minimum Inhibitory Concentrations of 138-169 against S. pyogenes

Compounds of Chapter-II exhibited promising activities against S. pyogenes are

listed below;

C2H5O

COOH

COOH

C2H5O N

O Cl

N

C2H5O

N

N

N

O Cl

N N

N

Cl

NO2

101 (MIC = 12.5 µg/ml) 105 (MIC = 100 µg/ml) 119 (MIC = 100 µg/ml)

C2H5O N

O Cl

N N

N

N

N

Cl

O2N

C2H5O

N

N

N

O Cl

N

Cl

C2H5O

N

N

N

O Cl

N

Cl

NO2

134 (MIC = 100 µg/ml) 141 (MIC = 62.5 µg/ml) 151 (MIC = 100 µg/ml)

C2H5O N

O Cl

NN

N

Cl

O2N

166 (MIC = 100 µg/ml)

4.1.2 Antifungal studies

Antifungal activity Chapter-II (methoxy derivatives)

Minimum Inhibitory Concentrations against C. albicans

From the antifungal results of intermediate 1-5, compound 1, 3 and 4 showed

good activity at 200 µg/ml compared to greseofulvin.

In series 1, compounds 6, 8, 12, 15, 18 and 20 possessed good activities at

200-250 µg/ml; whereas compound 17 showed very good activity at 100 µg/ml

compared to greseofulvin.

In series 2, compounds 24 and 32 possessed good activity at 100 µg/ml

compared to nystatin; whereas compounds 22, 23, 25, 27, 28, 34 and 35 possessed

good activities at 250 µg/ml compared to greseofulvin.

Fig. 17: Minimum Inhibitory Concentrations of 1-37 against C. albicans

In series 3, compound 42 and 44 possessed very good activity at 100 µg/ml

compared to nystatin; whereas compounds 41, 45 and 48 possessed poor activities at

1000 µg/ml while the remaining compounds showed moderate activity at 200-250

µg/ml. In series 4, compound 59 possessed very good activity at 100 µg/ml compared

to nystatin; whereas compounds 58 and 60 possessed poor activities at 1000 µg/ml

while the remaining compounds showed moderate activity at 200-250 µg/ml.

Fig. 18: Minimum Inhibitory Concentrations of 38-69 against C. albicans

The compounds showed promising antifungal activities against C. albicans are

shown below;

CH3O

N

N

N

O Cl

N N

N

ClCl

CH3O N

O Cl

N N

N

N

N

Cl

CH3O N

O Cl

N N

N

N

N

Cl Cl

17 (MIC = 100 µg/ml) 24 (MIC = 100 µg/ml) 32 (MIC = 100 µg/ml)

H3CO

N

N

N

O Cl

N

CH3

H3CO

N

N

N

O Cl

N

CH3

H3CO N

O Cl

NN

N

CH3

42 (MIC = 100 µg/ml) 59 (MIC = 100 µg/ml) 44 (MIC = 100 µg/ml)

Minimum Inhibitory Concentrations against A. niger

Compounds 1-5 possessed weak activity with greseufluvin and nystatin,. In

series 1, compounds 7, 12 and 19 possessed moderate activities at 200-250 µg/ml

whereas rest of compounds showed poor activity. In series 2, compounds 21, 27 and

34 possessed moderate activities at 200-250 µg/ml with greseufluvin and nystatin,

while others showed weak activity.

Fig. 19: Minimum Inhibitory Concentrations of 1-37 against A. niger

In series 3, compounds 38, 40, 46, 49 and 51 possessed moderate activities at

200-250 µg/ml. In series 4, compounds 58, 59, 62 and 66 possessed moderate

activities at 200-250 µg/ml with greseufluvin and nystatin; whereas other compound

showed weak activity.

Fig. 20: Minimum Inhibitory Concentrations of 38-69 against A. niger

Minimum Inhibitory Concentrations against A. clavatus

In series 1, compounds 7, 12 and 19 possessed moderate activities at 200-250

µg/ml. In series 2, compounds 22, 28 and 34 possessed moderate activities at 200-250

µg/ml compared to greseofulvin while other compounds possessed weak activity.

Fig. 21: Minimum Inhibitory Concentrations of 1-37 against A. clavatus

In series 3, compounds 39, 40, 43, 44, 45 and 51 possessed moderate activity

at 200-250 µg/ml. In series 4, compounds 54, 56, 66 and 10l possessed moderate

activities at 200-250 µg/ml, while others exhibited weak activity.

Fig. 22: Minimum Inhibitory Concentrations of 38-69 against A. clavatus

Antifungal activity Chapter-III (Ethoxy derivatives)

Minimum Inhibitory Concentrations against C. albicans

Compounds 104 very good activities at 250 µg/ml compared to greseofulvin.

In series 1, compound 112 and 117 possessed good activity at 250 µg/ml compared to

greseofulvin; whereas others possessed moderate to poor activities compared to

nystatin.

In series 2, compound 125 and 130 possessed good activity at 250 µg/ml

compared to greseofulvin; whereas remaining compounds moderate to poor activities.

Fig. 23: Minimum Inhibitory Concentrations of 101-137 against C. albicans

In series 3, compounds 142, 147 and 149 possessed good activities at 250 µg/ml.

In series 4, compounds 157 and 162 possessed good activities at 250

µg/ml.compounds 168 possessed good activities at 250 µg/ml compared to

greseofulvin

Fig. 24: Minimum Inhibitory Concentrations of 138-169 against C. albicans

Minimum Inhibitory Concentrations against A. niger

In series 1, all compounds possessed weak activities above 500 µg/ml. In

series 2, compounds 124 and 135 possessed moderate activities at 250 µg/ml; whereas

remaining compounds possessed weak activity at 500-1000 µg/ml.

Fig. 25: Minimum Inhibitory Concentrations of 101-137 against A. niger

In series 3, all compound possessed weak activities at 500-1000 µg/ml.

In series 4, compounds 166 possessed moderate activity at 250 µg/ml

compared to greseofulvin and nystatin while other compounds possessed weak

activities at 500-1000 µg/ml.

Fig. 26: Minimum Inhibitory Concentrations of 138-169 against A. niger

Minimum Inhibitory Concentrations against A. clavatus

In series 1 and 2, compounds 123 and 132 possessed moderate activity at 250

µg/ml while remaining compounds possessed weak activities at 500-1000 µg/ml;

Fig. 27: Minimum Inhibitory Concentrations of 101-137 against A. clavatus

In series 3, compounds 141, 148 and 151 possessed moderate activities at 250

µg/ml. In series 4, all the compounds possessed weak activities at 500-1000 µg/ml.

Fig. 28: Minimum Inhibitory Concentrations of 138-169 against A. clavatus

4.1.3 Antitubercular studies

Antitubercular activity of compounds of Chapter-II against Mycobacterium

tuberculosis H37Rv

The antimicrobial activity of compounds impelled us to screen the selected

compounds against Mycobacterium tuberculosis H37Rv. Compounds 9 very good

activity at 12.5 µg/ml as compared to rifampicin. Compounds 13 and 63 exhibited

good activity at 100-125 µg/ml as compared to rifampicin.

CH3O

N

N

N

O Cl

N N

N

Cl

CH3O

N

N

N

O Cl

N N

N

NO2

CH3O N

O Cl

NN

NCl

Cl

9 (MIC = 12.5 µg/ml) 13 (MIC = 125 µg/ml) 63 (MIC = 100 µg/ml)

Fig. 29: Minimum Inhibitory Concentrations of selected compound against M.

tuberculosis H37Rv

Antitubercular activity of compounds of Chapter-III against Mycobacterium

tuberculosis H37Rv

Compound 120 (2,6-Cl; 4-NO2) showed better activity against M. tuberculosis

H37Rv; whereas compounds 115 (4-NO2) and 137 (3-CH2-) showed good activity

when compared to rifampicin.

C2H5O

N

N

N

O Cl

N N

N

Cl

O2N

Cl

C2H5O

N

N

N

O Cl

N N

N

O2N

C2H5O N

O Cl

N

N N

N

120 (MIC = 12.5 µg/ml) 115 (MIC = 100 µg/ml) 137 (MIC = 100 µg/ml)

Fig. 30: Minimum Inhibitory Concentrations of selected compound against against M.

tuberculosis H37Rv

4.2 Overall conclusions

Minimal inhibitory concentrations of tested compounds showed that synthesis

of various 2-pyridones from β-aryl glutaconic acid and introduction of 1,2,4-

triazole, pyrrolidine and substituted aryl diazonium chlorides, variation of activity

was observed (increase or decrease) depending upon electronic properties of the

substituents. The MIC values showed that two isomers displayed varying activity

and are not comparable to each other.

Overall conclusions of Chapter-II and Chapter-III are described below:

Chapter-II (Methoxy derivatives)

• Chloro and nitro substituted derivatives displayed very good activities against E.

coli. Compounds 6 (-H), 7 (2-Cl), 38 (-H) and 64 (3,4-Cl) displayed very good

activities compared to ampicillin and chloramphenicol.

• Almost all the derivative except few ones showed weak activities to ciprofloxacin

and norfloxacin. Compounds possessed good activities against P. aeruginosa

compared to ampicillin.

• Chloro and nitro substituted derivatives displayed very good activities against S.

aureus. Compounds 3 (6-Cl), 8 (3-Cl), 13 (2-NO2), 23 (3-Cl), 28 (2-NO2), 40 (3-

Cl) 45 (2-NO2), 47 (4-NO2), 55 (3-Cl) and 60 (2-NO2) possessed very good

activity compared to ampicillin but moderate to weak when compared with

chloramphenicol, ciprofloxacin and norfloxacin.

• The result of activity against S. pyogenes was not found satisfactory when

compared to chloramphenicol, ciprofloxacin and norfloxacin, but moderate to

good activity was observed compared to ampicillin.

• Almost all compounds possessed very good activities against C. albicans

compared with greseofulvin; whereas chloro and methyl substituted derivatives 17

(3,4-Cl), 24 (4-Cl), 32 (3,4-Cl), 42 (2-CH3), 44 (4-CH3) and 59 (4-CH3) displayed

good activities compared with nystatin.

• Most of the compounds displayed weak activity against A. niger and A. clavatus

compared with control drugs nystatin and greseofulvin.

• Compound 9 (4-Cl) showed better activity against M. tuberculosis H37Rv;

whereas compounds 13 (2-NO2) and 63 (2,5-Cl) showed good activity compared

to rifampicin.

Chapter-III (Ethoxy derivatives)

• Chloro substituted derivatives displayed very good activities against E. coli.

Compounds 108 (3-Cl), 123 (3-Cl), 136 (3-CH2-) and 156 (4-Cl) displayed very

good activities while nitro substituted derivatives displayed good activities

compared to ampicillin and chloramphenicol.

• Compounds 121 (-H), 137 (3-CH2-), 141 (4-Cl), 163 (2,5-Cl) as well as nitro

substituted derivatives 114 (3-NO2), 120 (2,6-Cl; 4-NO2), 146 (2-NO2) and 167

(2,6-Cl; 4-NO2) displayed good activities against P. aeruginosa compared to

ampicillin but moderate activity was observed with chloramphenicol.

Almost all compounds exhibited poor activity to ciprofloxacin and norfloxacin.

• Glutaconic acid 101 displayed excellent activity compared against S. aureus.

Compounds 108 (3-Cl), 115 (4-NO2), 119 (4-Cl, 2-NO2), 130 (4-NO2) and 134 (4-

Cl, 2-NO2) showed very good activity compared to ampicillin but moderate to

ciprofloxacin and norfloxacin.

• Glutaconic acid 101 displayed excellent activity compared against S. pyogenes,

ciprofloxacin and norfloxacin. Compounds 141 (4-Cl) possessed very good

activity compared to ampicillin.

• Almost all compounds possessed good activities against C. albicans compared

with greseofulvin; whereas weak activities compared to nystatin.

• Most of the compounds displayed weak activity against A. niger and A. clavatus

compared with control drugs nystatin and greseofulvin.

• Compound 120 (2,6-Cl; 4-NO2) showed better activity against M. tuberculosis

H37Rv; whereas compounds 115 (4-NO2) and 137 (3-CH2-) showed good activity

compared to rifampicin.

Photographs showing the MIC of synthesized compounds at different concentrations using

Lowenstein-Jensen method against M. tuberculosis.

CONFERENCES ATTENDED AND PAPER PRESENTED:

• National Conference on Green Chemistry organized by Dept. of

Chemistry, VNSGU, Surat (Feb. 6-8, 2009)

• Gujarat Science Congress held at VNSGU, Surat (Feb 15, .2009)

• National workshop on “Environmental engineering” jointly organized by

Environ and TIFAC, Surat (Feb 2009)

• AICTE approved “Summer school on advance instrumental methods of

analysis” (Aug. 24-28, 2009)

• State level workshop on “Symmetry, group theory and spectroscopy” at

Navyug science college, Surat ( Sept 26-27, 2009)

• Indian Council of Chemists held at Hemchandracharya North Gujarat

University, Patan (Nov10, 2009): Young Scientist Award for best poster

presentation in Orgain Chemistry Section.

• 15 days workshop at School of Green Chemistry sponsored by DST ,

Madurai Kamrej University (Dec 14-27, 2009): Second prize for best

poster presentation

• Sixth All Gujarat Reserch Scholars Meet held in MSU, Vadodara (Jan. 31,

2010)

• Seminar on “Emerging trends in organic chemistry” organized by Sir P.T.

Sarvajanik College of Science, Surat (Feb 21, 2010)

• Seminar on “Recent trends in organic chemistry” organized by Sir P.T.

Sarvajanik College of Science, Surat (Dec 19, 2010)

• National Conference on “Role of chemistry in health and diseases”

organized by Dept. of Chemistry, Mithibai College, Mumbai in association

with the Indian Chemical Society (Jan 17-19, 2011)

• Two day Seminar sponsored by UGC on “Recent Advances in analytical

techniques for Pharmaceuticals” organized by Dept. of Pharmaceutical

Sciences, S.P. University, V.V. Nagar (March 18-19, 2011)

• One day Seminar sponsored by UGC on “Polymers and their

applications” organized by Dept. of Chemistry, VNSGU, Surat( March 28,

2011)

PAPER PUBLICATIONS:

• Synthesis of novel 6-Substtituted amino-4-(4-ethoxy phenyl)-1-phenyl-

2(H)-pyridinones via azo coupling.

N.B. Patel , R.D. Sharma & A.I. Gandhi; Monatsh Chem (2010) 141:1123-

1133.

• A Facile Route to Substituted 6-(4H-1,2,4-triazol-4-yl)-2(1H)-

pyridinones via Azo Coupling using Column Chromatography

N.B. Patel, Rakesh D. Sharma; Synthetic Communication-Taylor & Francis

(Communicated)

• Synthesis, characterization of substituted 6-(pyrrolidin-1-yl)-2(1H)-

pyridinones and their antibacterial, antifungal and antitubercular activity

N.B. Patel, Rakesh D. Sharma, Smita D. Rajani; Medicinal Chemisttry

Research- springer (Communicated)

• A Facile Route to 6-Substituted piperazinyl-2(H)-pyridinones via Azo

Coupling using Column Chromatography

N.B. Patel, R.D. Sharma & A.I. Gandhi; Chemistry of Heterocyclic

Compounds, springer (Communicated)