Insilico Design, Synthesis and Anticancer Activity of Novel Benzothiazole-Thiadiazole Hybrid Analogues As MPS1 Inhibitors

Human monopolar spindle 1 (MPS1) kinase (also known as TTK gene) is dual serine/threonine kinase that play dynamic role inspindle kinase assembly checkpoints (SAC) signalling pathways by controlling chromosomal alignment.Dysfunction of MPS1 found in different types of cancers like breast, thyroid, gastric, lungs etc. A series of novel benzothiazole-thiadiazole hybrid analogues were designed and screened using Insilico and In vitro methods. Insilico studies were performed by structure based virtual screening using Schrodinger Small-Molecule Drug Discovery suite. The Human monopolar spindle 1 (MPS1) kinase was found as most relevant target using Swiss Target Prediction. The molecular docking studies were performed on human monopolar spindle1 kinase protein obtained from the protein data bank. Fourteen compounds were screened on the basis of Insilico studies which were further synthesized and evaluated for anticancer activity. The anticancer screening of synthesized compounds was performed against colon cancer cell line CaCo-2 using MTT assay. We found six potent compounds which have IC50 value in the range between18-26µM. Promising results in Insilico and in vitro studies of these compounds shows, it could be further explored as novel MPS1 inhibitors.