title: Design, synthesis and in-vitro evaluation of novel tetrahydroquinoline carbamates as HIV-1 RT inhibitor and their antifungal activity.
abstract: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are vital class of drugs in treating HIV-1 infection, but drug resistance and toxicity drive the need for effective new inhibitors with potent antiviral activity, less toxicity and improved physicochemical properties. In the present study, twelve novel 1-(4-chlorophenyl)-2-(3,4-dihydroquinolin-1(2H)-yl)ethyl phenylcarbamate derivatives were designed as inhibitor of HIV-1 RT using the ligand based drug design approach and in-silico evaluated for drug-likeness properties. Designed compounds were synthesized, characterized and in-vitro evaluated for RT inhibitory activity against wild HIV-1 RT. Among these, four compounds (6b, 6i, 6j and 6l) exhibited significant inhibition of HIV-1 RT (IC50 ⩽ 20 μM). Among four compounds, most active compounds 6b and 6j inhibited the RT activity with IC50 8.12 and 5.42 μM respectively. Docking studies of compounds 6b and 6j were performed against wild HIV-1 RT in order to predict their putative binding mode with selected target. Further, cytotoxicity and anti-HIV activity of compounds 6b and 6j were evaluated on T lymphocytes (C8166 cells). All the synthesized compounds were also evaluated for antifungal activity against Candida albicans and Aspergillus niger fungal strains.
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. Electronic address: subhashsaininiper@gmail.com.
authors.forename: Subhash
authors.initials: S
authors.lastname: Chander
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India.
authors.forename: Penta
authors.initials: P
authors.lastname: Ashok
authors.affiliation: Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China. Electronic address: zhengyt@mail.kiz.ac.cn.
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.affiliation: Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India.
authors.forename: Krishnamohan S
authors.initials: KS
authors.lastname: Raja
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India.
authors.forename: Akash
authors.initials: A
authors.lastname: Taneja
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: Sankaranarayanan
authors.initials: S
authors.lastname: Murugesan
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001234:Aspergillus niger / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D062105:Molecular Docking Simulation; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C000613602:1-(4-chlorophenyl)-2-(3,4-dihydroquinolin-1(2H)-yl)ethyl 4-nitrophenylcarbamate; C000613601:1-(4-chlorophenyl)-2-(3,4-dihydroquinolin-1(2H)-yl)ethyl o-tolylcarbamate; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D002219:Carbamates; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase
keywords: Antifungal; Antiretroviral; Cytotoxicity; Docking; Drug-likeness; Reverse transcriptase; Tetrahydroquinoline