title: Synthesis and study of anti-HIV-1 RT activity of 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives.
abstract: In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC50≤25µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50values 8.62 and 6.87µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Chander
authors.affiliation: Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of ZoologyChinese Academy of Sciences, Kunming, Yunnan 650223, China; School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China.
authors.forename: Cheng-Run
authors.initials: CR
authors.lastname: Tang
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia.
authors.forename: Helmi Mohammed
authors.initials: HM
authors.lastname: Al-Maqtari
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia.
authors.forename: Joazaizulfazli
authors.initials: J
authors.lastname: Jamalis
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Penta
authors.affiliation: LCM Laboratory, FSO, University of Mohammed Premier, Oujda 60000, Morocco.
authors.forename: Taibi Ben
authors.initials: TB
authors.lastname: Hadda
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia.
authors.forename: Hasnah Mohd
authors.initials: HM
authors.lastname: Sirat
authors.affiliation: Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of ZoologyChinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. Electronic address: murugesan@pilani.bits-pilani.ac.in.
authors.forename: Murugesan
authors.initials: M
authors.lastname: Sankaranarayanan
mesh_terms: D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes; D004305:Dose-Response Relationship, Drug; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; D054303:HIV Reverse Transcriptase
keywords: Cytotoxicity; Docking; Glide; HIV; Reverse Transcriptase