1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Medicinal Chemistry & Drug Discovery Synthesis, Anticancer and Antimicrobial Evaluation of New (E)-N’-Benzylidene-2-(2-ethylpyridin-4-yl)-4-methylthiazole- 5-carbohydrazides Mahesh B. Muluk, [a] Sambhaji T. Dhumal, [b] Naziya N. M. A. Rehman, [c] Prashant P. Dixit, [c] Kiran R. Kharat, [d] and Kishan P. Haval* [a] In search of new anticancer and antimicrobial agents, herein we report the synthesis of new substituted (E)-N’-benzylidene- 2-(2-ethylpyridin-4-yl)-4-methyl thiazole-5-carbohydrazide de- rivatives (6a-n), starting from ethionamide. The newly synthe- sized compounds were characterized by 1 HNMR, 13 CNMR and HRMS analyses. All the synthesized compounds have been evaluated for their anticancer activity. Among fourteen synthe- sized compounds, five carbohydrazide derivatives have dis- played more promising anticancer activity against the lung carcinoma A-549 cells. Also, these compounds were screened for their in vitro antibacterial and antifungal activities. The three carbohydrazide derivatives have exhibited good anti- bacterial and antifungal activities. 1. Introduction Cancer is prominent cause of death worldwide. [1] Numerous treatments have been established to cure cancer such as chemotherapy, immunotherapy, radiotherapy and surgery. Chemotherapy is considered as a good choice for anticancer treatment. However, the high toxic effects of chemotherapeutic drugs are major problem in the treatment of cancer, [2] In addition, cancer cells develop resistance to chemotherapeutics, which is a primary reason of failure in chemotherapy. [3] The emerging newer infectious diseases and increasing number of multidrug resistant microbial pathogens are an important issues of immunosuppressed patients with AIDS and those undergoing anticancer therapy or organ transplants. [4] Therefore, there is a need of innovation and development of newer chemical structures having both anticancer and anti- microbial properties. [5] In recent literature, some carbohydra- zides have been reported as anticancer, [6] antimicrobial, [7] antioxidant, [8] antitubercular, [9] anti-inflammatory and analgesic [10] agents. Hydrazonyl pharmacophore is associated with profound biological activities, [11] viz anthelmintic and antimicrobial, [12] cyclooxygenase inhibitor, [13] antioxidant, [14] anti-HIV, [15] and antitubercular. [16] Some of the biologically active hydrazones, relevant to the present work has been shown in Figure 1. Pyridine-thiazole fused heterocyclic systems are common structural motifs with significant applications in medicinal chemistry. [17,18] The carbohydrazides clubbed with either pyridyl or thiazolyl moieties have shown significant anticancer and antimicrobial activities. The literature reveals that the carbohydrazides clubbed with both pyridyl and thiazolyl moieties have not been reported. Considering these observations and in continuation of our efforts to identify new bioactive compounds, [19] here it has been thought worthwhile to design and synthesize new hybrid carbohydrazides with thiazolyl and pyridyl scaffolds in a single molecular framework with hope to obtain the new molecules with enhanced anticancer activity. Herein, we reported the multistep synthesis of (E)-N’-benzylidene-2-(2-ethylpyridin-4-yl)-4-methyl thiazole-5- [a] M. B. Muluk, Dr. K. P. Haval Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada Univer- sity, SubCampus, Osmanabad-413501 (MS) India E-mail: havalkp@gmail.com [b] Dr. S. T. Dhumal Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada Univer- sity, Aurangabad-431004 (MS) India [c] N. N. M. A. Rehman, Dr. P. P. Dixit Department of Microbiology, Dr. Babasaheb Ambedkar Marathwada University, SubCampus, Osmanabad-413501 (MS) India [d] Dr. K. R. Kharat Department of Biotechnology, Deogiri College, Aurangabad-431005 (MS) India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201902030 Figure 1. Biologically active hydrazones relevant to the present work Full Papers DOI: 10.1002/slct.201902030 8993 ChemistrySelect 2019, 4,8993–8997 © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim