Objective: Studies of open-chain analogues of antimycin A as caspase inhibitors of apoptosis by molecular docking approach through computeraideddrug design. The noveltyof this studyis finding the potentialantimycinA33 analogues which structurally modified against caspases.Methods: In finding potential caspase inhibitor of apoptosis in colorectal cancer (CRC) by in silico approach has been utilized. Protein structure ofcaspase has been downloaded from Protein Data Bank (1SHJ). The minimized of caspase was ready for molecular docking analysis. Analogues ofantimycin A as lead compounds were designed and assessed using Molsoft drug-likeness. Both protein and lignan derivatives were docked withAutodock 4.2. The best docking score was shown by the lowest binding energy.3Results: Analogues of antimycin A has been done by evaluating their physicochemical properties as lead compounds. From this assessment, itshowed that analogue 2 (AMD2), intermediate amide 4 (AMD4) showed good compounds to be drug-likeness by following Lipinski's rule of five(RO5), while intermediate amide 3 (AMD3) and antimycin A3 (AMY3) showed cannot followed in Lipinski's RO5. From molecular docking result, themost favorable binding of caspase was AMD4 and AMD2 based on its energy that AMD4 (−7.34 kcal/mol) has the best binding interaction comparedto AMD2 (−7.33 kcal/mol), AMY3 (−7.26 kcal/mol), and AMD3 (−5.23 kcal/mol), respectively.3Conclusion: This studies demonstrated that the opened-chain analogues of antimycin AAMD2 and AMD4 as a promising candidates of caspaseinhibitor of apoptosis in CRC.Keywords: Open-chain analogue, Antimycin A3, Caspase, Apoptosis, Anticolorectal cancer.3
