Abstract
During the last five decades, a large number of BT (Benzothiazole) derivatives formed one of the eligible structures in medicinal chemistry as anticancer agents. Most of the studies reveal that various substitutions at specific positions on BT scaffold modulate the antitumor property. The potential of BTs encouraged us to synthesize a number of new 2-((5-substitutedbenzothiazol-2-yl)thio)-N’-(2-(4-(substitutedphenyl)ethylidene)acetohydrazide derivatives and investigate their probable anticancer activity. 4-Substitued benzaldehyde derivatives (1a–1e) were afforded by the reaction of appropriate secondary amine and 4-fluorobenzaldehyde in DMF. Equimolar quantitates of 5-substitutedbenzothiazole-2-thiol, ethyl chloroacetate and K2CO3 were refluxed in acetone to obtain 2-((5-substitutedbenzothiazol-2-yl)thio)acetate derivatives (2a,2b), which reacted with excess of hydrazine hydrate to get 2-((5-substitutebenzothiazol-2-yl)thio)acetohydrazides (3a,3b). In the last step, 2-((5-substitutedbenzothiazol-2-yl)thio)-N’-(4-substitutedbenzylidene)acetohydrazide derivatives (4a–4j) were synthesized by the reaction of 1a–1e and 3a–3b in EtOH. The anticancer activity of target compounds was evaluated in three steps. First, an MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed to observe cytotoxic activity of the compounds against carcinogenic C6 (Rat brain glioma cell line), A549 (Human lung adenocarcinoma epithelial cell line), MCF-7 (Human breast adenocarcinoma cell line), and HT-29 (Human colorectal adenocarcinoma cell line) cancer cell lines. Healthy NIH3T3 (Mouse embryo fibroblast cell line) cells were also subjected to MTT assay to determine selectivity of the compounds towards carcinogenic cell lines. Secondly, inhibitory effects of selected compounds 4d, 4e, and 4h on DNA synthesis of C6 cells were investigated. Finally, flow cytometric analysis were performed to identify the death pathway of the carcinogenic cells.
Highlights
Cancer is still one of the most common reasons of death worldwide
In light of the knowledge above and with a goal to discover a novel class of anticancer agents, we report the synthesis and antitumor effect of new compounds, including acylhydrazone moiety as a linker between BT and phenyl scaffolds
The compounds 4a–4j were synthesized as summarized in Scheme 1
Summary
Cancer is still one of the most common reasons of death worldwide. In spite of the widespread research and fast changes in the cancer therapy, there is still a rising need for new treatments [1].Discovery of new chemotherapeutics are of principal importance due to the essential capability of tumour cells to develop resistance to current agents. Cancer is still one of the most common reasons of death worldwide. In spite of the widespread research and fast changes in the cancer therapy, there is still a rising need for new treatments [1]. Discovery of new chemotherapeutics are of principal importance due to the essential capability of tumour cells to develop resistance to current agents. The progress of multiple drug resistance to antitumor drugs is a major problem in the chemotherapy. Research for the recognition of novel agents for the managing of cancer is at the critical level [2]. Benzothiazole (BT) compounds display the anticancer activity by acting on various biological targets. Some important instances related to these biotargets are replication and mitosis inhibitors [3], Molecules 2018, 23, 1054; doi:10.3390/molecules23051054 www.mdpi.com/journal/molecules
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