PENAMBATAN MOLEKUL TURUNAN BENZOFURAN SEBAGAI INHIBITOR ENZIM Polyketide synthase 13 M. tuberculosis RESISTEN
DOI:
https://doi.org/10.47219/ath.v11i1.412Keywords:
molecular docking, modifikasi sruktur, Pks13, TAM, TBCAbstract
Tuberkulosis (TB) merupakan penyakit penyebab kematian terbesar ke-2 di dunia setelah Covid-19. Peningkatan kasus dan prevalensi TB berkaitan dengan resistensi Mycobacterium tuberculosis terhadap obat. Ketidakpatuhan pasien terhadap rejimen obat salah satu penyebab resistensi. Kebutuhan klinis mendesak pengembangan obat untuk tuberculosis dengan menyasar target baru. Polyketide synthase13 (Pks13) satu enzim yang jarang ditargetkan pada pengobatan tuberkulosis. Satu senyawa bioaktif yang dapat dikembangkan dalam mengatasi resistan obat adalah senyawa turunan benzofuran. Namun, ditemukan toksisitas tidak bisa diterima pada TAM (senyawa Turunan benzofuran) sehingga masih sangat memerlukan modifikasi struktur. Tujuan penelitian ini adalah untuk mengeksplorasi dan memodifikasi struktur senyawa turunan benzofuran untuk menemukan kandidat potensial obat baru tuberkulosis. Modifikasi senyawa baru menggunakan subtituen skema Topliss. Selanjutnya dilakukan analisis Lipinski’s menggunakan SWISSADME dan penambatan molekuler terhadap enzim Mtb Pks 13 menggunakan iGem-Dock. Hasil penelitian menunjukan senyawa hasil modifikasi (senyawa 16a) memiliki energi ikatan (delta G) yang lebih rendah (-9,03 kkal/moL) jika dibandingkan senyawa/ligan reference (TAM16) (-7,77 kkal/moL) dan memenuhi aturan Lipinski’s. Senyawa hasil modifikasi berpotensi untuk dilakukan sintesis dan di uji secara in vitro pada enzim Pks 13.
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