Synthesis of piperazinyl benzothiazole/benzoxazole derivatives coupled with 1,3,4-oxadiazole-2-thiol: novel hybrid heter
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Med Chem Res DOI 10.1007/s00044-013-0510-y
ORIGINAL RESEARCH
Synthesis of piperazinyl benzothiazole/benzoxazole derivatives coupled with 1,3,4-oxadiazole-2-thiol: novel hybrid heterocycles as anticancer agents M. S. R. Murty • B. Ramalingeswara Rao Mohana Rao Katiki • Lekshmi R. Nath • Ruby John Anto
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Received: 2 December 2012 / Accepted: 19 January 2013 Ó Springer Science+Business Media New York 2013
Abstract The synthesis of a series of substituted 2-(piperazin-1-yl)benzothiazole/benzoxazole coupled with 1,3,4oxadiazole-2-thiol pharmacophore (8a–t) is described using a three carbon spacer (Jones and Helm, Drugs 69:1903– 1910, 2009). The structures of the compounds were confirmed by NMR and mass spectral data. All the synthesized compounds have been evaluated for their cytotoxicity towards five human cancer cell lines of different origins, viz. MCF-7 (Breast), HeLa (Cervical), HepG2 (Liver), A431 (Skin) and A549 (Lung), and IC50 values were determined. Among the compounds tested, 8j and 8t displayed maximum cytotoxic activity. A431 was the most sensitive cell line against the compounds studied, followed by MCF7, A549, HepG2 and HeLa. Keywords Piperazine Benzothiazole Benzoxazole 1,3,4-Oxadiazole Anticancer MTT assay
Introduction Cancer is a serious disease that can affect almost every tissue lineage in the human body (Varmus, 2006) and poses great challenges to medical science. Hence, there is need for the discovery and development of novel antitumor drug M. S. R. Murty (&) B. Ramalingeswara Rao M. R. Katiki Discovery Laboratory, Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India e-mail: [email protected]; [email protected] L. R. Nath R. J. Anto (&) Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram 695014, Kerala, India e-mail: [email protected]
molecules which could effectively inhibit proliferative pathways. Antiproliferative and cytotoxic drugs play a major role in cancer therapy, whether used alone or in combination with other treatments such as surgery, radiation and biological therapy. Nowadays, combination chemotherapy using drugs with different mechanisms of action is being adopted to treat cancer so that the toxicity of treatment can be minimized. Therefore, a single molecule containing more than one pharmacophore, each with different mode of action, could be beneficial for the treatment of cancer. Long-chain arylpiperazine (LCAP) derivatives represent one of the important class of therapeutic agents in medicinal chemistry. Generally, arylpiperazine moiety is a good template for many different biological targets. In recent years, extensive research has been focused on developing novel piperazine derivatives to improve anticancer activities. Among these attempts, modifying the piperazine moiety with some functional groups such as introducing an alkyl chain constituted by two- to four carbon atoms linked to the N - 1 of piperazine mo
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