Design Synthesis and Biological Evaluation of Dithiocarbamate Substituted 2-Aminobenzothiazole Derivatives as Proviral Integration Site of Moloney Murine Leukaemia Virus 1 Kinase Inhibitors

Abstract

In the present study, we intended to synthesize novel derivatives against Proviral Integration site of Moloney murine leukaemia virus 1 kinase, a biomarker over expressed in numerous malignancies. A novel series of derivatives containing dithiocarbamate moiety as a side chain at the second position of 2-amino benzothiazole nucleus were synthesized and characterized by spectral analysis. From the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide Assay performed, compounds 4a, 4c and 4h of the series emerged as potent anticancer agents against SK-OV-3 cell lines with half-maximal inhibitory concentration value of 34.52±0.5 μM, 34.28±0.06 μM and 29.17±0.66 μM, respectively (p<0.05) compared to standard drug doxorubicin’s half-maximal inhibitory concentration value 17.07±0.05 μM. From the anti-mitotic activity studies all the compounds showed good to moderate activity with half-maximal inhibitory concentration values ranging from 1.88±0.66 to 20.91±0.34 μM, (p<0.05). The evaluation of in silico absorption, distribution, metabolism, excretion, and toxicity and molecular descriptors, proved that the synthesized compounds posses drug like properties and are safer to the normal cells. From the molecular docking studies, compounds 4a, 4c, 4h showed good binding affinity with PIM 1 Kinase protein and retained required amino acid interaction similar to the co-crystal. Hence, this study proves 2 amino benzothiazole dithiocarbamate derivatives can be used as encouraging leads as PIM 1 Kinase inhibitors).