SKRIPSI

HESTINING PUSPAWENI

UJI AKTIVITAS SENYAWA DALAM

TANAMAN YANG BERPOTENSI SEBAGAI

ANTIDIABETES MELLITUS TERHADAP

RESEPTORNYA SECARA IN SILICO

(Terhadap Tanaman Momordica charantia Fructus dan

Tamandus indica Folium)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2018

ii

Lembar Pengesahan

UJI AKTIVITAS SENYAWA DALAM TANAMAN YANG BERPOTENSI

SEBAGAI ANTIDIABETES MELLITUS TERHADAP RESEPTORNYA

SECARA IN SILICO

(Terhadap Tanaman Momordica charantia Fructus dan Tamandus indica Folium)

SKRIPSI

Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada Program Studi Farmasi

Fakultas Ilmu Kesehatan

Universitas Muhammadiyah Malang

2018

Oleh :

HESTINING PUSPAWENI

201410410311203

Disetujui Oleh :

Pembimbing I Pembimbing II

Engrid Juni Astuti, M. Farm., Apt

NIP UMM. 11216120589

Sovia Aprina Basuki, M.Farm.,M.Si Apt.

NIP UMM. 11408040452

iii

Lembar Pengujian

UJI AKTIVITAS SENYAWA DALAM TANAMAN YANG BERPOTENSI

SEBAGAI ANTIDIABETES MELLITUS TERHADAP RESEPTORNYA

SECARA IN SILICO

(Terhadap Tanaman Momordica charantia Fructus dan Tamandus indica Folium)

USULAN SKRIPSI

Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada Program Studi Farmasi

Fakultas Ilmu Kesehatan

Universitas Muhammadiyah Malang

2018

Oleh :

HESTINING PUSPAWENI

201410410311203

Disetujui Oleh :

Penguji I

Sovia Aprina Basuki, M.Farm., M.Si., Apt

NIP UMM. 11408040452

Penguji II

Engrid Juni Astuti, M.Farm., Apt

NIP UMM. 11216120589

Penguji III

Dian Ermawati, M.Farm., Apt

NIP UMM. 11209070481

Penguji IV

Dra. Uswatun Chasanah, M.Kes., Apt

NIP UMM. 114070448

iv

KATA PENGANTAR

Segala puji bagi Allah SWT yang telah melimpahkan rahmat, taufik, dan

hidayah-Nya bagi seluruh hamba sehingga skripsi ini dapat terselesaikan dengan

sebaik-baiknya. Sholawat serta salam semoga senantiasa tercurah kepada junjungan

Nabi Besar Muhammad SAW, kesejahteraan semoga terlimpah kepada keluarga,

sahabat serta orang-orang yang beriman.

Dengan terselesaikannya skripsi yang berjudul UJI AKTIVITAS

SENYAWA DALAM TANAMAN YANG BERPOTENSI SEBAGAI

ANTIDIABETES MELLITUS TERHADAP RESEPTORNYA SECARA IN

SILICO (Terhadap Tanaman Momordica charantia Fructus dan Tamandus

indica Folium) ini, perkenankanlah saya selaku penulis mengucapkan terimakasih

yang sebesar-besarnya kepada :

1. Allah SWT yang telah memberikan segala kenikmatan, kelancaran dan

kemudahan bagi saya dalam menyelesaikan skripsi ini.

2. Faqih Ruhyanudin, M.Kep., Sp.Kep.MB. selaku Dekan Fakultas Ilmu

Kesehatan Universitas Muhammadiyah Malang yang telah memberikan

kesempatan penulis belajar di Fakultas Ilmu Kesehatan Universitas

Muhammadiyah Malang.

3. Dian Ermawati, S.Farm., Apt. selaku Ketua Program studi Farmasi Universitas

Muhammadiyah Malang yang telah memberi motifasi dan kesempatan penulis

belajar di Program Studi Farmasi Universitas Muhammadiyah Malang.

4. Sovia Aprina Basuki, S.Farm, M.Si., Apt. selaku pembimbing I dan Engrid

Juni Astuti M.Farm., Apt. selaku pembimbing II yang selalu meluangkan

waktu untuk membimbing dan memberikan arahan-arahan yang terbaik demi

kesempurnaan skripsi ini.

5. Dian Ermawati, S.Farm., Apt. dan Dra. Uswatun Chasanah, M.Kes.,Apt.,

selaku dosen penguji yang telah memberikan masukan kepada saya demi

kesempurnaan skripsi ini.

v

6. Ahmad Sobrun Jamil. S.Si, M.P. selaku dosen wali yang senantiasa

memberikan nasihat-nasihat yang bermanfaat bagi saya demi kesuksesan

dalam menuntut ilmu.

7. M. Artabah Muchlisin, M. Farm. Selaku dosen pembimbing in silico yang

senantiasa bersabar dalam membimbing kami selama penelitian skripsi.

8. Para Bapak Ibu Dosen Program Studi Farmasi yang telah mengajarkan kepada

saya pengetahuan yang sangat bermanfaat sehingga saya dapat menyelesaikan

pendidikan sarjana.

9. Ibundaku yang tercinta yang senantiasa memberikan doa, cinta, kasih sayang,

perhatian, kebahagiaan, kepercayaan, nasihat-nasihat, dukungan baik moral

ataupun materi yang sangatlah bermanfaat bagi anakmu ini.

10. Kakak-kakak tercinta kak Hastin dan kak Heri yang selalu memberi semangat,

dan perhatian.

11. Teman kelompok in silico devi, muftia, gita, hana, rotul, azizah trimakasih atas

kerjasama, dukungan kesabaran dan kebersamaan dalm suka duka

mengerjakan skripsi.

12. Sahabatku devi dan retno yang senantiasa memberiku semangat disaat rasa

malas melanda.

13. Semua pihak yang tidak dapat disebutkan satu-persatu, terimakasih atas

bantuan, dukungan yang telah diberikan dalam penyelesaian skripsi ini

Semoga Allah SWT selalu melimpahkan rahmat-Nya atas segala budi baik

yang telah diberikan. Akhirnya, semoga skripsi ini dapat berguna bagi

pengembangan ilmu pengetahuan khususnya ilmu kefarmasian.

Malang, 28 Mei 2018

Penulis

x

DAFTAR ISI

Lembar Pengesahan ............................................................................................ ii

Lembar Pengujian ............................................................................................... iii

KATA PENGANTAR ........................................................................................ iv

RINGKASAN ..................................................................................................... vi

ABSTRAK .......................................................................................................... viii

DAFTAR ISI ....................................................................................................... x

DAFTAR GAMBAR .......................................................................................... xii

DAFTAR TABEL ............................................................................................... xiii

DAFTAR LAMPIRAN ....................................................................................... xiv

BAB I PENDAHULUAN ................................................................................... 1

1.1 Latar Belakang ........................................................................................ 1

1.2 Rumusan Masalah ................................................................................... 3

1.3 Tujuan Penelitian ..................................................................................... 3

BAB II TINJAUAN PUSTAKA ......................................................................... 5

2.1 Reseptor ................................................................................................... 5

2.1.1 Asam Amino ........................................................................................... 5

2.2 Farmakodinamika Obat ........................................................................... 7

2.2.1 Mekanisme Kerja Obat ............................................................................ 7

2.2.2 Jenis Ikatan Obat dengan Reseptor ......................................................... 8

2.2.3 Hubungan Struktur dan Interaksi Obat dengan Reseptor ........................ 13

2.3 Diabetes Mellitus ..................................................................................... 15

2.3.1 Definisi Diabetes Mellitus ....................................................................... 15

2.3.2 Sekresi Insulin oleh Sel beta Pankreas .................................................... 17

2.3.3 Patofisiologi Diabetes Mellitus Tipe 1 .................................................... 19

2.3.4 Patofisiologi Diabetes Mellitus Tipe 2 .................................................... 21

2.3.5 Golongan Obat Antidiabetes ................................................................... 24

2.4 Pemanfaatan Obat Antidiabetes Mellitus ................................................ 29

2.4.1 Buah Pare ................................................................................................ 29

2.4.2 Daun Asam Jawa ..................................................................................... 31

2.5 Senyawa Metabolit Sekunder .................................................................. 33

2.6 Tinjauan Tentang Metode In Silico ......................................................... 33

2.6.1 Definisi Uji In Silico ............................................................................... 34

2.6.2 Perangkat Lunak dalam Uji In Silico ...................................................... 34

2.6.3 Jenis Metode in Silico ............................................................................. 36

2.6.4 Database Pendukung Perangkat Lunak Uji in Silico .............................. 38

BAB III KERANGKA KONSEPTUAL ............................................................. 40

BAB IV METODE PENELITIAN ..................................................................... 42

4.1 Jenis Penelitian ........................................................................................ 42

xi

4.2 Tempat dan Waktu Penelitian ................................................................. 42

4.3 Kreteria Inklusi dan Eksklusi Penelitian ................................................. 42

4.3.1 Kreteria Inklusi ........................................................................................ 42

4.3.2 Kreteria Eksklusi ..................................................................................... 42

4.4 Alat dan Bahan Penelitian ....................................................................... 43

4.4.1 Alat Penelitian ......................................................................................... 43

4.4.2 Bahan Penelitian ...................................................................................... 43

4.5 Prosedur Penelitian .................................................................................. 44

4.5.1 Preparasi Senyawa ................................................................................... 44

4.5.2 Pemisahan Ligan dengan Reseptor.......................................................... 45

4.5.3 Preparasi Ligan dengan Reseptor ............................................................ 46

4.5.4 Validasi Metode Docking ........................................................................ 47

4.5.5 Docking Senyawa Uji .............................................................................. 48

4.5.6 Visualisasi Hasil Docking ....................................................................... 48

4.5.7 Rancangan Hasil Docking ....................................................................... 49

2.5.8 Uji Statistika Anova ................................................................................ 49

BAB V HASIL PENELITIAN ........................................................................... 50

5.1 Hasil Validasi Reseptor ........................................................................... 50

5.2 Hasil Pengukuran Energi Afinitas Ligan dan Reseptor........................... 51

5.3 Visualisasi Hasil Docking Ligan dan Reseptor ....................................... 61

5.4 Hasil Uji Statistika Anova ....................................................................... 86

5.5 Gugus Farmakofor Hasil Docking Reseptor dan Ligan .......................... 89

BAB VI PEMBAHASAN .................................................................................. 110

BAB VII KESIMPULAN ................................................................................... 118

7.1 Kesimpulan .............................................................................................. 118

7.2 Saran ........................................................................................................ 119

DAFTAR PUSTAKA ......................................................................................... 120

LAMPIRAN 1 ..................................................................................................... 128

xii

DAFTAR GAMBAR

Gambar Halaman

Gambar 2.1 Struktur Asam Amino ..................................................................... 6

Gambar 2.2 Ikatan σ ............................................................................................ 11

Gambar 2.3 Ikatan π ............................................................................................ 12

Gambar 2.4 Interaksi Anion- π............................................................................ 12

Gambar 2.5 Interaksi Kation π ............................................................................ 13

Gambar 2.6 Sekresi Insulin oleh Rangsang Glukosa .......................................... 17

Gambar 2.7 Patofisiologi Diabetes Mellitus Tipe 1 ........................................... 22

Gambar 2.8 Struktur Sulfonolurea ...................................................................... 24

Gambar 2.9 Mekanisme Sufonilurea .................................................................. 25

Gambar 2.10 Stuktur Meglitinid ......................................................................... 26

Gambar 2.11 Struktur Biguanid .......................................................................... 27

Gambar 2.12 Struktur Insulin .............................................................................. 28

Gambar 2.13 Buah Pare ...................................................................................... 30

Gambar 2.14 Daun Asam Jawa ........................................................................... 32

xiii

DAFTAR TABEL

Tabel Halaman

Tabel II.1 Pengelompokan Asam Amino berdasarkan Sifat kelarutan ............... 6

Tabel II.2 Pengelompokan Asam Amino Berdasarkan Gugus R ........................ 6

Tabel II.3 Tipe Ikatan Kimia Beresta Contoh dan Kekuatannya ........................ 11

Tabel V.1 Hasil Validasi Metode Docking Reseptor dan Ligan ......................... 50

Tabel V.2 Hasil Pengukuran Energi Afinitas Reseptor dan Ligan ..................... 51

Tabel V.3 Hasil Visualisasi Daun Asam Jawa .................................................... 61

Tabel V.4 Hasil Visualisasi Buah Pare ............................................................... 70

Tabel V.5 Hasil Analisis Statistika One Way Anova Tamarindus indica Folium 86

Tabel V.6 Hasil Analisis Statistika One Way Anova Momordica charantia

Fructus ................................................................................................................ 87

Tabel V.7 Gugus Farmakofor hasil Docking Reseptor dan Ligan ...................... 89

xiv

DAFTAR LAMPIRAN

Lampiran Halaman

Lampiran 1 Daftar Riwayat Hidup ..................................................................... 129

Lampiran 2 Surat Pernyataan ............................................................................. 130

Lampiran 3 Surat Tugas ..................................................................................... 131

Lampuran 4 Kandungan Senyawa Kimia Tanaman Obat .................................. 132

Lampiran 5 Visualisasi Hasil Docking ............................................................... 138

Lampiran 6 Analisis Data SPSS One Way Anova ............................................. 199

120

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