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Synthesis and evaluation of isonicotinoyl hydrazone derivatives as antimycobacterial and anticancer agents

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Abstract

A new series of isonicotinoyl hydrazone derivatives (3a–3o) have been synthesized, characterized and evaluated for in vitro antimycobacterial activity against M. tuberculosis H37Rv and two clinical isolates using tetrazolium microplate assay (TEMA). Some of these compounds showed moderate to good antimycobacterial activity at micro molar concentrations. Among them, 3k and 3m were the most potent analogues with an inhibition concentration at 0.59 and 0.65 μM, respectively, against M. tuberculosis H37Rv compared to parent drug, isoniazid (0.57 μM). Additionally, all the synthesized compounds were subjected to in vitro anticancer activity against human colorectal cancer cell lines (HCT 116). Compounds 3b and 3l displayed antiproliferative activity at inhibitory concentration 3.1 and 0.29 μM, respectively, when compared to standard, 5-fluorouracil (5 μM). These results can be considered as an important start point for the rational design of new leads for antitubercular and anticancer drug discovery.

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Acknowledgments

The authors wish to thank Suriyati Mohamed and Dr. Siti Suraiya Md. Noor, Department of Medical Microbiology and Parasitology, School of Medical Sciences, University of Science Malaysia (USM) for providing MTB clinical isolates. The authors also wish to thank EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, USM for assisting in conducting in vitro anticancer assay. This research is supported by USM under the Research University Grant (1001/PFARMASI/815005). Naveen Kumar and Thaigarajan are thankful to University of Science Malaysia, for providing USM-fellowship.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, University of Science Malaysia, 11800, Minden, Pulau Pinang, Malaysia

    H. S. Naveen Kumar, Thaigarajan Parumasivam, Fatimah Jumaat, Pazilah Ibrahim, Mohd. Zaini Asmawi & Amirin Sadikun

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  1. H. S. Naveen Kumar
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  2. Thaigarajan Parumasivam
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  3. Fatimah Jumaat
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  5. Mohd. Zaini Asmawi
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Correspondence to H. S. Naveen Kumar.

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Naveen Kumar, H.S., Parumasivam, T., Jumaat, F. et al. Synthesis and evaluation of isonicotinoyl hydrazone derivatives as antimycobacterial and anticancer agents. Med Chem Res 23, 269–279 (2014). https://doi.org/10.1007/s00044-013-0632-2

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  • DOI: https://doi.org/10.1007/s00044-013-0632-2

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