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

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 μM, 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).