Bulbine frutescens phytochemicals as novel ABC-transporter inhibitor:a molecular docking and molecular dynamics simulation study  

作　　者：Prem Prakash Kushwaha Santosh Kumar Maurya Amit Singh Kumari Sunita Prajapati Atul Kumar Singh Mohd Shuaib Shashank Kumar 

机构地区：[1]Molecular Signaling&Drug Discovery Laboratory,Department of Biochemistry,Central University of Punjab,Bathinda 151401,India [2]Department of Computational Sciences,Central University of Punjab,Bathinda 151401,India.

出　　处：《Journal of Cancer Metastasis and Treatment》2021年第1期20-32,共13页癌症转移与治疗（英文版）

基　　金：support from the Indian Council of Medical Research(ICMR),India in the form of ICMR Senior Research fellowship.SK acknowledges the University Grants Commission(UGC),India and Department of Science and Technology(DST),India for providing financial support in the form of UGC-BSR Research Start-Up-Grant[No.F.30-372/2017(BSR)]and DST-SERB Grant(EEQ/2016/000350)respectively.SK also acknowledges DST,India for providing the Departmental DST-FIST grant to the Department of Biochemistry,Central University of Punjab,India.AKS and MS acknowledges CSIR and ICMR,India funding agencies respectively for providing financial assistance in the form of a Senior Research Fellowship.KSP acknowledge DBT,India funding agencies for providing financial assistance in the form of Junior Research Fellowship.

摘　　要：Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were used to retrieve the ligands and target protein structure.The molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics simulation.Results:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter protein.Docking score analysis revealed that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead compounds.Conclusion:The in-silico study demonstrated that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.

关 键 词：Cancer drug resistance ABC-TRANSPORTER natural inhibitors Bulbine frutescens MM-GBSA 

分 类 号：G63[文化科学—教育学]