Synthesis and thymidine phosphorylase inhibition studies of 5-chlorobenzothiazole derivatives

Benzothiazole and their derivatives have been previously reported to exhibit antitumor, antimicrobial, antiviral and anticonvulsant activities [1]. Thymidine phosphorylase inhibitors have attracted great attention due to their ability to suppress the tumors formation. In our ongoing research, a series of 5-chlorobenzothiazole derivatives (1 – 10) have been synthesized in good to excellent yields (80 – 90%) and their thymidine phosphorylase inhibition potential has also been evaluated. The synthesized compounds showed moderate thymidine phosphorylase inhibitory activity with IC50 values ranging from 19.60 ± 0.45 to 93.50 ± 2.88µM, and 7- deazaxanthine (7DX) was used as a standard(IC50 38.68 ± 4.42). Compound 1, 4-(5-chlorobenzo[d]thiazol-2-yl)benzene-1,3-diol and compound 2, 5-chloro-2-(4-chlorophenyl)benzo[d]thiazole showed the lowest IC50 values of 19.60 ± 0.45µM and 23.40 ± 0.68µM, compared to the standard inhibitor. These compound showed better phosphorylase inhibition activity as compared to 7-deazaxanthine [2].

Fig. 1: Structure compound of Benzothiazole

Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM) and Atta ur Rahman Institute for Natural Products Discovery, are acknowledged for providing laboratory facilities.

References:

[1] Srivastava SK, Yadav R, Srivastava SD. Indian J Chem 2004; 43: 399 – 405.

[2] Sohail AS, Shahzad A, Yar M, Bajda M, Jadoon B, Khan ZA, Naqvi SAR, Shaikh AJ, Hayat K, Mahmmod A, Mahmood N, Filipek S. Bioorganic & Medicinal Chemistry 2014; 22: 1008 – 1015