SKRIPSI

AZIZA RATNA SARIp

UJI AKTIVITAS SENYAWA DALAM TANAMAN BERPOTENSI SEBAGAI OBAT

BATUK DENGAN METODE IN SILICO (Pada tanaman Glycyrhiza glabra Radix dan

Zingiber officinale Rhizoma)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2018

ii

Lembar Pengesahan

UJI AKTIVITAS SENYAWA DALAM TANAMAN BERPOTENSI SEBAGAI OBAT BATUK DENGAN

METODE IN SILICO (Pada tanaman Glycyrhiza glabra Radix dan Zingiber officinale

Rhizoma)

SKRIPSI

Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan

Universitas Muhammadiyah Malang 2018

Oleh :

AZIZA RATNA SARI NIM : 201410410311018

Disetujui Oleh :

iii

Lembar Pengujian

UJI AKTIVITAS SENYAWA DALAM TANAMAN BERPOTENSI SEBAGAI OBAT BATUK DENGAN

METODE IN SILICO (Pada tanaman Glycyrhiza glabra Radix dan Zingiber officinale

Rhizoma)

SKRIPSI

Telah diuji dan dipertahankan di depan tim penguji pada tanggal

28 Mei 2018

Oleh:

AZIZA RATNA SARI

NIM : 201410410311018

Disetujui Oleh :

iv

KATA PENGANTAR

Alhamdulillah puji syukur kehadirat Allah Subhanallahu Wa Ta’ala yang

senantiasa memberikan rahmat, hidayah, serta karunia-Nya. Hanya kepada-Nya

lah kita memohon pertolongan dan memohon ampunan. Dan kepada-Nya lah

tempat berlindung dari kejahatan jiwa dan keburukan perbuatan. Sholawat serta

salam tak lupa mari kita haturkan kepada junjungan kita nabi Muhammad SAW,

semoga kita semua mendapat syafa’atnya di yaumul kiyamah nanti.

Penelitian tugas akhir ini berjudul “Uji Aktivitas Senyawa dalam

Tanaman Berpotensi sebagai Obat Batuk dengan Metode in Silico (Pada

tanaman Glycyrhiza glabra Radix dan Zingiber officinale Rhizoma) ”, diajukan

untuk memenuhi persyaratan Pendidikan Sarjana Farmasi Fakultas Ilmu

Kesehatan Universitas Muhammadiyah Malang.

Pada kesempatan ini, penulis ingin menyampaikan terimakasih kepada :

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

Kesehatan Universitas Muhammadiyah Malang atas ilmu dan

bimbingannya selama di Fakultas Ilmu Kesehatan UMM.

2. Hj. Dian Ermawati, S.Farm., Apt., M.Farm., selaku Ketua Program Studi

Farmasi Universitas Muhammadiyah Malang atas ilmu dan bimbingannya

selama di Fakultas Ilmu Kesehatan UMM.

3. Sovia Aprina Basuki, S. Farm., M. Si., Apt., selaku dosen pembimbing 1

dan Engrid Juni Astuti, M.Farm., Apt. Selaku dosen pembimbing 2, yang

telah memberikan bimbingan dalam penyusunan skripsi dengan penuh

v

kesabaran dan kebaikan hati sehingga penulis dapat menyelesaikan

penelitian ini dengan baik.

4. Hj. Dian Ermawati, S.Farm., Apt., M.Farm., selaku dosen penguji 1 dan

Dra. Uswatun Chasanah, Apt., M.Kes, selaku dosen penguji 2, yang telah

memberikan masukan dalam perbaikan skripsi ini serta ilmu yang sangat

berharga.

5. Biro Skripsi Universitas Muhammadiyah Malang yang telah membantu

dalam segala persyaratan skripsi dan Seluruh Staf TU yang telah

membantu dalam menyediakan segala keperluan untuk kelancaran proses

skripsi.

6. Ika Ratna Hidayati, S. Farm., M. Farm., Apt. selaku dosen wali yang telah

sabar membimbing dan memberi dorongan moril selama menyelesaikan

program pendidikan sarjana Farmasi.

7. Seluruh Dosen dan Staf pengajar Farmasi UMM yang telah mendidik dan

mengajarkan ilmu pengetahuan selama penulis menempuh pendidikan

sarjana Farmasi di Universitas Muhammadiyah Malang.

8. Keluarga besar, kedua orang tua, Bapak Syed Aziz dan Ibu Niswati Diana

Sari, Ibu mertua Rohati, Bapak mertua Alm. Suryadi serta kakak Azizka

Junaidah Sari, kakak ipar Bang Ryno Melja, Mbak Lely Mayasari, Mbak

Novi Sintia Sari, dan adik Arjun Indila Aprianda yang telah memberikan

kepercayaan, dukungan, semangat, kasih sayang, pengorbanan, serta doa

sehingga penulis dapat menyelesaikan skripsi tepat waktu dan menjadi

Sarjana Farmasi.

vi

9. Tidak lupa pula kepada keluarga kecil tercintaku, Suamiku Anton

Kurniawan dan Anakku Khanza Azzahra Humayrah yang selalu

memberikan kasih sayang dan support untuk menyelesaikan skripsi tepat

waktu.

10. M. Artabah Muchlisin, M.Farm, yang telah bersedia meluangkan waktu

untuk memberikan ilmu dan membantu dalam kelancaran skripsi..

11. Seluruh Tim skripsi in silico, Devi Sesyarani, Gita A. F., Hanan

Rumaisah, Hestining Puspaweni, Masrurotul Muflihah dan Muftia

Mu’alimin termakasih atas kerjasama, dukungan, kesabaran, dan

kebersamaan dalamsetiap suka dan duka selama mengerjakan skripsi.

12. Para sahabat Afina Naufal dan Windy Risqe A.P yang telah memberi

semangat, dukungan, kasih sayang dan terimakasih untuk 4 tahun yang

berharga bersama dalam suka dan duka.

13. Serta semua pihak dari dalam maupun luar yang telah membantu sehingga

terselesaikannya skripsi ini.

Dalam menyelesaikan skripsi ini tentunya tidak lepas dari keterbatasan

penulis. Oleh karena itu, penulis sangat mengharapkan saran dan masukan yang

membangun sehingga nantinya dapat memberikan hasil yang terbaik.

Wassalamualaikum Warahmatullahi Wabarakatuh.

Malang, 28 Mei 2018

Penulis

xi

DAFTAR ISI LEMBAR PENGESAHAN .......................................................................... ii

LEMBAR PENGUJI .................................................................................... iii

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

RINGKASAN ................................................................................................ vii

ABSTRAK .................................................................................................... ix

DAFTAR ISI .................................................................................................. xi

DAFTAR TABEL ......................................................................................... xiv

DAFTAR GAMBAR .................................................................................... xv

DAFTAR LAMPIRAN ................................................................................. xvi

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

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

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

1.3 Tujuan Penelitian ............................................................................... 4

1.4 Manfaat Penelitian ............................................................................. 4

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

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

2.1.1 Asam Amino ....................................................................................... 7

2.2 Farmakodinamika Obat ....................................................................... 9

2.2.1 Mekanisme Kerja Obat ........................................................................ 9

2.2.2 Jenis Ikatan Obat dan Reseptor ........................................................... 10

2.2.3 Teori Interaksi Obat-Reseptor .............................................................. 12

2.3 Batuk ................................................................................................... 14

2.3.1 Definisi Batuk ...................................................................................... 14

2.3.2 Etiologi Batuk ..................................................................................... 14

2.3.3 Patofisiologi Batuk ............................................................................. 15

2.3.4 Klasifikasi Batuk ............................................................................... 16

2.4 Obat Batuk ............................................................................................ 17

2.5 Pemanfaatan Tanaman Untuk Obat Batuk ........................................... 24

2.6 Senyawa Metabolit Sekunder Tanaman ............................................... 28

2.7 Tinjauan Tentang Metode Uji In Silico ............................................. 29

2.7.1 Definisi Metode In Silico ..................................................................... 29

xii

2.7.2 Perangkat Lunak Dalam Uji in Silico ................................................... 29

2.7.3 Jenis Metode in Silico .......................................................................... 31

2.7.4 Database Pendukung Perangkat Lunak Uji in Silico ........................... 33

BAB III KERANGKA KONSEPTUAL ...................................................... 36

3.1 Kerangka Konseptual Penelitian ......................................................... 36

BAB IV METODE PENELITIAN .............................................................. 38

4.1 Jenis Penelitian ..................................................................................... 38

4.2 Tempat dan Waktu Penelitian ............................................................. 38

4.3 Alat dan Bahan Penelitian .................................................................. 38

4.3.1 Alat Penelitian .................................................................................... 38

4.3.2 Bahan Penelitian ................................................................................. 38

4.4 Kriteria Inklusi dan Eksklusi .............................................................. 39

4.4.1 Kriteria Inklusi .................................................................................... 39

4.4.2 Kriteria Eksklusi .................................................................................. 39

4.5 Prosedur Penelitian .............................................................................. 40

4.5.1 Preparasi Senyawa ................................................................................ 40

4.5.2 Pemisahan Ligan dengan Reseptor ................................................... 41

4.5.3 Preparasi Makromolekul Dan Ligan .................................................. 41

4.5.4 Validasi Reseptor dan Obat .................................................................. 42

4.5.5 Docking Ligan Senyawa Pembanding dan Senyawa Uji .................... 43

4.5.6 Visualisasi Reseptor Obat dan Senyawa Tanaman .............................. 44

4.5.7 Uji Statistik Anova ............................................................................... 44

BAB V HASIL PENELITIAN ................................................................... 45

5.1 Hasil Validasi Ligan Asli Dengan Reseptor ..................................... 45

5.2 Hasil Pengukuran Energi Afinitas Ligan-Reseptor . ........................... 46

5.3 Visualisasi Hasil Docking Ligan-Reseptor ......................................... 67

5.4 Hasil Visualisasi Gugus Farmakofor .............................................. 176

5.5 Hasil Uji Statistika .......................................................................... 214

BAB VI PEMBAHASAN .......................................................................... 220

BAB VII KESIMPULAN ............................................................................. 232

7.1 Kesimpulan ...................................................................................... 232

7.2 Saran .................................................................................................. 232

xiii

DAFTAR PUSTAKA .................................................................................... 233

LAMPIRAN ................................................................................................ 243

xiv

DAFTAR TABEL

Tabel Halaman

Tabel II.1 Reseptor Obat ............................................................................. 6

Tabel II.2 Pengelompokan Asam Amino Berdasarkan Sifat Kelarutan ...... 8

Tabel II.3 Pengelompokan Asam Amino Berdasakan Gugus R .................. 8

Tabel IV.1 Tabel Reseptor Obat Batuk ........................................................ 41

Tabel V.1 Hasil Validasi Reseptor dan Obat ............................................... 45

Tabel V.2 Hasil Docking Reseptor dan Senyawa Tanaman Zingiberis

Rhizome .................................................................................... 46

Tabel V.3 Hasil Docking Reseptor dan Senyawa Tanaman Glycyrrhiza

Radix ...................................................................................... 47

Tabel V.4 Hasil Visualisasi Jenis Ikatan dan Residu Asam Amino Reseptor

Obat dan Senyawa Pada Tanaman Zingiberis rhizome ............. 67

Tabel V.5 Hasil Visualisasi Jenis Ikatan dan Residu Asam Amino Reseptor

Obat dan Senyawa Pada Tanaman Glycyrrhiza radix ............... 101

Tabel V.6 Hasil Visualisasi Gugus Farmakofor Pada Tanaman Zingiberis

rhizome ...................................................................................... 176

Tabel V.7 Hasil Visualisasi Gugus Farmakofor Pada Tanaman Glycyrrhiza

Glabra ...................................................................................... 190

Tabel V.8 Hasil Uji Statistika Pada Tanaman Zingiberis rhizome ............. 214

Tabel V.9 Hasil Uji Statistika Pada Tanaman Glycyrrhiza glabra ............ 215

xv

DAFTAR GAMBAR

Gambar Halaman

Gambar 2.1 Macam Asam Amino Yang Terdapat Pada Protein .................. 8

Gambar 2.2 Patofisiologi Batuk ................................................................. 15

Gambar 2.3 Struktur Dextromethorpan ..................................................... 17

Gambar 2.4 Struktur Codeine ...................................................................... 18

Gambar 2.5 Struktur Benzonatate ............................................................... 18

Gambar 2.6 Struktur Guaiphenesin ........................................................... 19

Gambar 2.7 Struktur Bromhexine ............................................................... 20

Gambar 2.8 Struktur Ambroxol ................................................................. 21

Gambar 2.9 Struktur Dipenhydramine dan Chlorpheniramine .................... 21

Gambar 2.10 Struktur Salbutamol ................................................................. 22

Gambar 2.11 Rhizoma Zingiber officinale .................................................... 24

Gambar 2.12 Tanaman Glycyrrhiza glabra .................................................. 26

Gambar 2.13 Logo Protein Data Bank .......................................................... 33

Gambar 2.14 Logo Pubchem ........................................................................ 34

Gambar 2.15 Logo Drugbank ...................................................................... 34

Gambar 3.1 Kerangka Konseptual Penelitian ............................................ 36

xvi

DAFTAR LAMPIRAN

Lampiran Halaman

1. Biodata Mahasiswa ..................................................................................... 243

2. Surat Pernyataan ......................................................................................... 244

3. Surat Tugas ................................................................................................ 245

4. Form Plagiasi ............................................................................................. 246

4. Daftar Senyawa Tanaman ........................................................................... 247

5. Data Statistika Energi Afinitas Ligan Pembanding dan Ligan Uji ........... 266

6. Visualisasi Senyawa dan Reseptor .............................................................. 281

233

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