Keywords
N-(Benzoyl)-N’-4-metoxyphenylthiourea
Analgesic activity
Toxicity.
Abstract
Abstrak Latar belakang : Senyawa N-(Benzoil)-N’-4-metoksifeniltiourea mempunyai gugus farmakofor yang sama dengan asam mefenamat yang mempunyai aktivitas sebagai analgesik, sehingga layak dijadikan senyawa induk untuk dikembangkan lebih lanjut melalui modifikasi struktur. Tujuan : Penelitian ini bertujuan untuk memprediksi aktivitas analgesik dan toksisitas dari duapuluh senyawa turunan N-(Benzoil)-N’-4-metoksifeniltiourea sebagai calon obat analgesik. Salah satu mekanisme kerja turunan N-(Benzoil)-N’-4-metoksifeniltiourea sebagai analgesik adalah menghambat COX2, yang berperan penting dalam mengubah asam arakidonat menjadi prostaglandin. Metode : Aktivitas biologis dapat diprediksi melalui pemodelan molekul yang disebut uji in silico,menggunakan program molecular operating environment (MOE) sedangkan toksisitas dapat diprediksi menggunakan program pkCSM. Uji in silico dilakukan dengan melakukan docking senyawa yang akan diprediksi aktivitasnya dengan target reseptor COX2, PDB 5IKR. Hasil : Hasil docking berupa energi ikatan digambarkan dengan nila Score (S). Senyawa dengan nilai S kecil berarti mempunyai ikatan ligan-reseptor yang stabil dan diprediksi mempunyai aktivitas yang besar. Dari hasil uji in silico disimpulkan bahwa turunan N-(benzoil)-N’-4-metoksifeniltiourea diprediksi menimbulkan toksisitas relative rendah, dan mempunyai aktivitas yang lebih besar dibandingkan asam mefenamat. Simpulan : N-(Etoksibenzoil)-N’-4-metoksifeniltiourea diprediksi mempunyai aktivitas analgesik paling besar sehingga senyawa terpilih untuk disintesis dan dikembangkan lebih lanjut. Abstract Background: The compound N-(benzoyl)-N'-4-methoxyphenylthiourea has the same pharmacophore group as mefenamic acid which has analgesic activity, so it is suitable to be used as a parent compound for further development through structural modification. Objective: This study aims to predict the analgesic activity and toxicity of twenty N-(benzoyl)-N'-4-methoxyphenylthiourea derivative compounds as candidate analgesic drugs. One of the mechanisms of action of the N-(benzoyl)-N'-4-methoxyphenylthiourea derivative as an analgesic is to inhibit COX2, which plays an important role in converting arachidonic acid into prostaglandins. Method: Biological activity can be predicted through molecular modeling called in silico testing, using the molecular operating environment (MOE) program, while toxicity can be predicted using the pkCSM program. The in silico test is carried out by docking the compound whose activity will be predicted with the target receptor COX2, PDB ID 5IKR. Results: The docking results in the form of bond energy are described by the value Score (S). A compound with a small S value means it has a stable ligand-receptor bond and is predicted to have large activity. From the in silico test results, it was concluded that the N-(benzoyl)-N'-4-methoxyphenylthiourea derivative is predicted to cause relatively low toxicity, and has greater activity than mefenamic acid. Conclusion: N-(Ethoxybenzoyl)-N'-4-methoxyphenylthiourea are predicted to have the greatest analgesic activity so the compounds were selected for synthesis and further development.References
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