Senyawa Antikanker Dan Insektisida Dari Genus Aglaia

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Senyawa Antikanker Dan Insektisida Dari Genus Aglaia DESI HARNETI PUTRI HUSPA SENYAWA ANTIKANKER DAN INSEKTISIDA DARI GENUS AGLAIA UNPAD PRESS SENYAWA ANTIKANKER DAN INSEKTISIDA DARI GENUS AGLAIA -i- -ii- DESI HARNETI PUTRI HUSPA SENYAWA ANTIKANKER DAN INSEKTISIDA DARI GENUS AGLAIA UNPAD PRESS -iii- TIM PENGARAH Ganjar Kurnia Mahfud Arifin, Engkus Kuswarno Memed Sueb TIM EDITOR Wilson Nadeak (Koordinator), Tuhpawana P. Sendjaja Fatimah Djajasudarma, Benito A. Kurnani Denie Heriyadi, Wahya, Cece Sobarna Dian Indira Judul : Senyawa Antikanker dan Insektisida dari Genus Aglaia Penulis : Desi Harneti Putri Huspa UNPAD PRESS Copyright © 2009 ISBN 978-979-3985-55-8 -iv- PENGANTAR Alhamdulillah, segala puji dan syukur selalu terpanjatkan hanya untuk Allah SWT sehingga penyusun dapat menyelesaikan draft buku ini. Buku ini berjudul “Senyawa Antikanker dan Insektisida dari Genus Aglaia” yang diajukan sebagai salah satu pertanggungjawaban penerima Hibah Penelitian Mahasiswa Doktor Tahun 2009 (SK Rektor Nomor 1607/H6.1/KEP/HK/2009) di Program Doktor Pascasarjana FMIPA Universitas Padjadjaran. Pada kesempatan kali ini penyusun mengucapkan terima kasih kepada: Prof. Dr. Roekmiati Tjokronegoro, Ir., Prof. Dr. Anas Subarnas, M.Sc. dan Dr. Unang Suptaman selaku Tim Promotor, yang telah meluangkan waktu, tenaga dan pikirannya untuk membimbing penyusun dalam penyusunan buku ini. Penyusun menyadari sepenuhnya bahwa penyusunan buku ini jauh dari kata sempurna karena keterbatasan ilmu, pengetahuan dan pengalaman yang penyusun miliki. Masukan dan kritik yang membangun sangat penyusun harapkan demi kemajuan penyusun khususnya dan kita semua pada umumnya. Akhir kata, semoga penyusunan karya tulis ini dapat bermanfaat bagi kita semua dan selanjutnya dapat dipergunakan sebagaimana mestinya. Bandung, Desember 2009 Penyusun -v- -vi- DAFTAR ISI Halaman BAB I SEL KANKER MERUSAK ALAT 1 TUBUH BAB II TINJAUAN UMUM 5 Kanker dan Sel Tumor 5 Tinjauan Tumbuhan Meliaceae dan Aglaia 24 Kandungan Kimia pada Tumbuhan Aglaia 32 Senyawa Aktif Sitotoksik dari Tumbuhan Aglaia 40 BAB III SENYAWA ANTIKANKER TURUNAN 1H-SIKLOPENTA[b]BENZOFURAN DARI TANAMAN Aglaia elliptica 47 Aglaia elliptica 47 Mekanisme sitotoksik pada tanaman Aglaia elliptica 50 BAB IV AKTIVITAS ANTIKANKER SENYAWA ODORIN DAN ODORINOL DARI TUMBUHAN AGLAIA ODORATA 59 Aglaia odorata 59 Taksonomi Aglaia odorata 60 -vii- Halaman Kandungan kimia tumbuhan Aglaia odorata 61 Bahan-bahan dan metode penelitian 64 BAB V SENYAWA SITOTOKSIK DARI 77 KULIT BATANG Aglaia crassinervia Aglaia crassinervia 77 Taksonomi Aglaia crassinervia 78 Eksperimen 79 Kandungan kimia tumbuhan Aglaia 81 crassinervia Evaluasi Aktivitas Biologis 97 BAB VI AKTIVITAS INSEKTISIDA SENYAWA FLAVAGLIN DARI KULIT BATANG AGLAIA EDULIS TERHADAP LARVA SPODOPTERA LITTORALIS 103 Aglaia edulis 103 Spodoptera littoralis 107 Bahan dan Metode 112 Hasil dan Pembahasan 114 DAFTAR PUSTAKA 131 INDEKS 141 -viii- GLOSARI Alkaloid : Senyawa dalam arti luas bersifat basa, mengandung unsur nitrogen heterosiklik, berstruktur molekul komplek, mempunyai aktifitas farmakologi. Antikanker : Zat yang dapat menghambat atau membunuh sel kanker DNA : Deoxyribonucleic acid. Asam nukleat yang terdapat dalam inti sel, yaitu di dalam kromosom. Glukosa : Suatu jenis monosakarida golongan heksosa dengan satu gugus aldehid. Perbedaan galaktosa dengan glukosa ada pada letak gugus –OH di atom C no. 4. IC50 : Inhibition Consentration 50%. Konsentrasi yang dapat menghambat pertumbuhan sel sebanyak 50%. Kanker : atau karsinoma adalah pembentukan jaringan baru yang abnormal dan bersifat ganas (maligne). Lemak : Ester dari gliserol dan asam-asam lemak Leukemia : Kanker darah Mutasi : Kesalahan dalam replikasi, sehingga mengakibatkan kerusakan DNA secara permanen. ppm : Part per million, bagian per juta -ix- Proliferasi Suatu kelompok sel yang tiba – tiba menjadi liar dan memperbanyak diri secara pesat dan terus menerus. RNA : Ribonucleic acid. Asam nukleat yang terdapat di luar inti sel, yaitu di dalam sitoplasma. Sel kanker : adalah kumpulan sel yang secara genetik menghancurkan sel inang dan berkembang menjadi sel yang tidak normal. Sitotoksik : Racun sel Steroid : Senyawa lipid yang bukan golongan ester dengan struktur dasar yang terdiri dari 17 atom karbon yang berbentuk 4 cincin. Triterpen : Terpena dengan jumlah atom kurang lebih 30. Terdiri dari gabungan ekor-kepala unit isoprena. Secara biosintesis diturunkan dari hidrokarbon C30 alisiklik, yaitu skualena. Toksisitas : Daya racun -x- -xi- BAB I SEL KANKER MERUSAK ALAT TUBUH MENURUT Organisasi Kesehatan Dunia, WHO, setiap tahun jumlah penderita kanker di dunia bertambah 6,25 juta orang. Dalam 10 tahun mendatang diperkirakan 9 juta orang akan meninggal setiap tahun akibat kanker. Dua pertiga dari penderita kanker di dunia akan berada di negara-negara yang sedang berkembang. Sel kanker adalah kumpulan sel yang secara genetik menghancurkan sel inang dan berkembang menjadi sel yang tidak normal. Penyebab terjadinya sel kanker karena beberapa sel tidak dapat merespons mekanisme regulasi kerja sel. Konsekuensinya sel tersebut akan terus berkembang karena akan mengambil nutrien dari sel normal (McKee and McKee, 1999). Sel kanker dapat membuat anak sebar (metastasis) ke bagian alat tubuh lain yang jauh dari tempat asalnya melalui pembuluh darah dan pembuluh getah bening dan tumbuh kanker baru di tempat lain. Penyusupan sel kanker ke jaringan sehat pada alat tubuh lainnya dapat merusak alat tubuh tersebut sehingga fungsi alat tersebut menjadi terganggu. Kanker dapat menimpa semua orang pada semua bagian tubuh dan pada semua golongan (1) 2 Desi Harneti P.H. umur. Kanker dapat timbul pada pria, wanita maupun anak-anak. Walaupun kanker dapat timbul pada anak- anak, tetapi lebih sering timbul pada orang dewasa, terutama pada orang yang berusia 40 tahun ke atas. Ini disebabkan oleh ketidakseimbangan hormon dan proses menua atau kemunduran pertumbuhan sel. Akhir-akhir ini kemoterapi menjadi salah satu terobosan dalam pengendalian kanker. Meskipun penemuan dan pemakaian kemoterapi menunjang hasil yang bagus, tetapi toksisitas dan efek sampingnya sangat besar (Siswandono, 1993). Bahan-bahan alam mempunyai prospek sebagai penghambat pertumbuhan sel kanker. Distribusi aktivitas antikanker sangat luas dalam tumbuh-tumbuhan. Pendekatan yang sering dilakukan dalam mencari zat kandungan yang berkhasiat sebagai antikanker dari tanaman ialah dengan kemotaksonomi tanaman, yakni tanaman yang termasuk dalam takson tertentu dan mempunyai kemiripan tanda- tanda anatomi, histologi, morfologi dan kemiripan dalam zat kandungannya. Farnsworth melaporkan bahwa 400 spesies tanaman dalam genus 97 famili mempunyai aktivitas sebagai penghambat tumor (Farnsworth, 196). Berbagai zat kandungan yang berkhasiat sebagai antikanker dan beberapa tanaman telah berhasil diisolasi oleh Mc Laughlin et al, di mana pencarian senyawa bioaktif tersebut dilakukan setelah dalam praskrining aktivitas terhadap ekstrak tanaman menunjukkan hasil positif atau aktif. Indonesia adalah negara kedua di dunia yang memiliki keanekaragaman hayati terbanyak termasuk tumbuhan Meliaceae yang hanya tumbuh di daerah Sel Kanker Merusak Alat Tubuh 3 tropis. Aglaia adalah genus terbesar dari keluarga Meliaceae, yang terdiri dari kurang lebih 130 spesies yang tersebar terutama di daerah Indo-Malaysian, Cina Selatan dan Kepulauan Pasifik. Aglaia adalah salah satu genus dari keluarga Meliaceae yang sangat potensil sebagai sumber senyawa antikanker turunan rokaglat, bisamida dan triterpenoid. Senyawa rokaglaol dan aglaiaglabretol B yang diisolasi dari Aglaia crassinervia teruji bersifat antikanker (Su, 2006). Lima senyawa turunan lignan benzofuran yang berhasil diisolasi dari A. elliptica terbukti dapat menghambat pertumbuhan sel kanker manusia (Lee, 1998). Janprasert et al. (1993) berhasil mengidentifikasi senyawa aktif yang bersifat antikanker dari ranting A. odorata sebagai rokaglamida. Sampai tahun 2001, para ilmuwan telah berhasil mengisolasi sebanyak 52 senyawa turunan rokaglamida. Aktivitas ekstrak bagian tanaman Aglaia selain dapat bersifat sebagai insektisidal dapat juga bersifat sebagai antimakan dan antikanker (Proksch et al.,2001). Aglafolin (metil rokaglat) yang diisolasi dari A. elliptifolia Merr. dapat menghambat pertumbuhan sel kanker (Ko et al.,1992). Aglaiastatin dan rokaglaol, menunjukkan dapat mengurangi jumlah sel kanker dengan cara menghambat sintesis proteinnya. Perusahaan obat Australia Cerylid Biosciences menyatakan bahwa senyawa yang terdapat pada tanaman A.lepthantha dapat membunuh 20 jenis sel kanker termasuk sel kanker yang menyebabkan kanker otak, payudara dan melanoma . Kandungan senyawa yang sama juga terdapat pada A. silvestris (Ohse et al.,1996). Sampai akhir tahun 2006, lebih 30 spesies Aglaia telah dilaporkan kandungan kimianya. Kandungan utama 4 Desi Harneti P.H. metabolit sekunder dari genus ini adalah benzo[b]oxepines, bisamid, siklopenta[b]benzofuran, siklopenta[b]benzopiran, lignan, steroid pregnan. Senyawa-senyawa turunan siklopenta[b]benzofuran (turunan rokaglat) telah dilaporkan secara signifikan dapat menghambat sel kanker manusia (Su, 2006; Lee, 1998). BAB II TINJAUAN UMUM Kanker dan Sel Tumor KANKER atau karsinoma adalah pembentukan jaringan baru yang abnormal dan bersifat ganas (maligne). Suatu kelompok sel yang tiba – tiba menjadi liar dan memperbanyak diri secara pesat dan terus menerus (proliferasi). Kanker terbentuk karena adanya mutasi pada biosintesis sel, yaitu kekeliruan urutan DNA karena terpotong, tersubstitusi atau ada pengaturan kembali, adanya adisi dan integrasi bahan genetik virus ke dalam gen
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