Pemodelan Molekul Turunan p-Metoksi sinnamoil Hidrazida Sebagai Inhibitor Checkpoint Kinase 1 dan Inhibitor Aromatase secara In silico

Abstract

AbstrakPengembangan obat antikanker dari derivat Etil-p-metoksi Sinamat (EPMS) terus dilakukan untuk memperoleh senyawa yang memiliki level apoptosis sel kanker yang tinggi dengan efek samping yang minimal. Senyawa turunan p-Metoksisinnamoil hidrazida yang diperoleh dari modifikasi struktur dari EPMS ditambatkan dengan enzim Check Point Kinase 1 (2YWP) dan enzim Aromatase (3S7S) dengan menggunakan software Molegro Virtual Docker (MVD) Ver.5.5. Parameter penambatan yang digunakan yaitu nilai Rerank score native ligand dibandingkan dengan rerank score senyawa turunan p-Metoksisinnamoil hidrazida. Senyawa 4b dan 4c memiliki nilai rerank score -99,98 kkal/mol dan -99,80 kkal/mol yang lebih rendah dari native ligand A42 dalam menghambat enzim check point kinase 1. Senyawa turunan p-Metoksisinnamoil hidrazida memiliki nilai rerank score yang lebih besar dibandingkan native ligan EXM dalam menghambat enzim aromatase. Senyawa turunan p-Metoksisinnamoil hidrazida terutama senyawa 4b dan 4c memiliki mekanisme antikanker dengan jalur menghambat enzim check point kinase 1 dan tidak memiliki aktivitas dalam menghambat enzim aromatase. AbstractThe development of anticancer drugs from ethyl p-methoxycinnamate (EPMC) derivatives has been done to compounds high activity in inducing cancer cells apoptosis and minimal side effects. p-Methoxycinnamoyl hydrazide derivates, modified from EPMC structure, were docked into the ligand-binding pocket of Check point kinase 1 enzymes (2YWP) and the aromatase enzyme (3S7S) using software Molegro Virtual Docker (MVD) Ver.5.5. We compared the Rerank score of native ligand with p-Methoxycinnamoyl hydrazide derivates. Rerank scores of compounds 4b and 4c Kcal/mol) were lower than the native ligand A42 in inhibiting the enzyme checkpoint kinase 1. Rerank values of p-Methoxycinnamoyl hydrazide derivate compounds were greater than the native ligand EXM in inhibiting the enzyme aromatase. p-Methoxycinnamoyl hydrazide derivate compounds, especially compounds 4b and 4c, had anticancer mechanism by inhibiting the checkpoint kinase 1 enzyme pathway and showed no activity in inhibiting the aromatase enzyme.

Synthesis, <i>In Vitro</i> Anticancer Activity and <i>In Silico</i> Study of some Benzylidene Hydrazide Derivatives

“…1). Anthranilic acid was reacting with benzoyl chloride in the presence of pyridine, generated benzoxaxine 1 through nucleophilic substitution of an amino group from anthranilic acid to carbonyl group of benzoyl chloride and followed by condensation [10,11]. Subsequent reaction with hydrazine hydrate produced compound 2, which can be confirmed from the 1 H-NMR and its mass spectra.…”

“…After gaining the crystal structure of 1M17 and its irreversible inhibitor, the receptor-ligand complexes were assessed in its active cavity [6]. The procedure of this evaluation based on the reference [10]. The RS obtained from in silico study can be interpreted as a prediction bonding interactions between drugs and its receptors.…”