Rational design and synthesis of novel thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Murugesan, Vanangamudi
Makwana, Nandini Suryawanshi, Rahul Saxena, Reshu Tripathi, Rajkamal Paranjape, Ramesh Kulkarni, Smita Katti, S B |
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| Date |
2014-08-12T06:41:54Z
2014-08-12T06:41:54Z 2014 |
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| Identifier |
Bioorganic & Medicinal Chemistry, 2014, 22(12), 3159–3170
http://hdl.handle.net/123456789/1361 |
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| Description |
A series of novel thiazolidin-4-one analogues, characterized by different substitution patterns at positions C-2 and N-3 of the thiazolidin-4-one scaffold for anti-HIV-1 activity has been investigated. Most of the compounds showed anti-HIV-1 activity at micromolar concentrations when tested in TZM-bl cells in vitro. Among the thirty-three compounds tested, compound 16 was the most potent inhibitor of HIV-1 replication against HIV-1IIIB, HIV-1ADA5, HIV-1UG070 and HIV-1VB59 (EC50 = 0.02, 0.08, 0.08 and 0.08 µM, respectively) with selectivity index (SI = 6940, 1735, 1692 and 1692) against tested viral strains, respectively. The results of the present study suggested that the substitution of the nitro group at 6' position of the C-2 phenyl ring and 2'',6''-dimethylpyridin-2-yl at the N-3 position of thiazolidin-4-one had a major impact on the anti-HIV-1 activity and was found to lower cytotoxicity. The substitution of the heteroaryl ring with bromo group and bicyclic heteroaryl ring at N-3 thiazolidin-4-one was found to lower anti-HIV-1 activity and increase cytotoxicity. The undertaken docking studies thus facilitated the identification of crucial interactions between the HIV-1 RT enzyme and thiazolidin-4-one inhibitors, which can be used to design new potential inhibitors.
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890555 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI Communication No. 8660
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| Subject |
Thiazolidin-4-Ones
Anti-HIV-1 Activity HIV-1 Reverse Transcriptase NNRTIs |
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| Title |
Rational design and synthesis of novel thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors
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| Type |
Article
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