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Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new pyrazolylthiazole derivatives

MEDICINAL CHEMISTRY RESEARCH (2017)

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MEDICINAL CHEMISTRY RESEARCH
卷 26, 期 10, 页码 2653-2665

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SPRINGER BIRKHAUSER
DOI: 10.1007/s00044-017-1963-1

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Anti-HIV activity; Antiproliferative activity; Crystal structure; NNRTIs; 1,3-Thiazole; Pyrazole

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Chemistry, Medicinal

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The development of new HIV-1 non-nucleoside reverse transcriptase inhibitors offers the possibility of generating novel structures of increased potency. Based on the bioisosteric principle, new series of N'-benzylidene-2-(5-(4-chlorophenyl)-3-phenyl-4,5-dihydropyrazol-1-yl)thiazole-4-carbohydrazide schiff bases 5a-x containing 1,3-thiazole clubbed with 2-pyrazoline was synthesized and characterized by spectroscopic techniques. The structure of the synthesized compounds was unambiguously confirmed by single-crystal X-ray diffraction analysis of compound 5k. All the new analogs were evaluated in vitro for antiviral activity against the replication of HIV-1 and HIV-2 in MT4 cells using MTT assay. The results showed that only compounds 5n, and 5r possess potent activity against HIV-1 replication (IC50 = 0.50, 0.45 mu M, SI = 3 and 5), respectively. None of the compounds are active against HIV-2. Furthermore, compounds 5a, 5i, 5n, and 5r were evaluated for their antiproliferative activity against two solid tumor-derived cell lines consisting MCF-7 (breast cancer) and Hep-G2 (human hepatocarcinoma).

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