Synthesis, biological screening and ADME prediction of benzylindole derivatives as novel anti-HIV-1, anti-fungal and ant
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Med Chem Res (2013) 22:4633–4640 DOI 10.1007/s00044-012-0463-6
ORIGINAL RESEARCH
Synthesis, biological screening and ADME prediction of benzylindole derivatives as novel anti-HIV-1, anti-fungal and anti-bacterial agents A. M. Kashid • P. N. Dube • P. G. Alkutkar • K. G. Bothara • S. N. Mokale • S. C. Dhawale
Received: 2 July 2012 / Accepted: 31 December 2012 / Published online: 17 January 2013 Ó Springer Science+Business Media New York 2013
Abstract Present study is focused on design, synthesis, and biological evaluation of substituted benzylindole derivatives as anti-HIV, anti-fungal, and anti-bacterial agents. Out of the reported compounds, compound B1 and B2 showed potent Anti-HIV activity, whereas compound B1–B4 showed good anti-fungal and anti-bacterial activity. ADME properties of benzylindol analogs were analyzed using Qikprop 2.5 tool of Schrodinger. Keywords HIV-1 Reverse transcriptase inhibitor Benzylindol ADME prediction
Introduction It has been recently reported that more than 33 million of people were infected worldwide with human immunodeficiency virus (HIV-1). The overall number of people living with HIV has increased as a result of new infections and the beneficial effects of the more widely available highly
A. M. Kashid (&) P. N. Dube P. G. Alkutkar K. G. Bothara Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmacy, Narhe, Pune 411041, Maharashtra, India e-mail: [email protected] S. N. Mokale Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India S. C. Dhawale Department of Pharmaceutical Chemistry, School of Pharmacy, SRTM University, Nanded, Maharashtra, India
active anti-retroviral therapy (HAART), which employs a combinational use of drugs (Este and Cihlar, 2010). Currently, FDA-approved anti-HIV drugs belong to seven different groups: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs) (Mehellou and De Clercq, 2010). Although the HAART has brought about a substantial decrease in the death rate, changing AIDS from a rapidly lethal disease into a chronic manageable condition, the retroviral infection can be only temporarily controlled but not eradicated since, HIV-1 becomes almost undetectable in the plasma for more than 2 years, persisting in reservoirs. Furthermore, the HAART efficacy has been limited by the emergence of drug-resistant viral strains, drug-toxicity, and the poor ability of patients to adhere to the prescribed therapy and costs, so a refining of the current therapies and the developing of new therapeutic paradigms are still warranted (Sechi et al., 2009). NNRTIs are a structurally diverse group of compounds which binds to the viral enzyme RT, where it interacts with a specific allosteric non-substrate binding pocket site. NNRTIs resistance mutations arise rapidly a
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