Design and Synthesis of Polycyclic Acridin-(9-yl-Amino)Thiazol-5-yl)-2H-Chromen-2-One Derivatives: As Antiproliferative and Anti-TB Pharmacophores

Abstract

A series of novel acridine-thiazole bridged coumarin derivatives 3a–3i were designed, synthesized and subjected for their in-vitro antiproliferative activity on human breast cancer (MDA-MB-231), lung cancer (A-549) and colon cancer (HT29) cell lines. In case of human breast (MDA-MB-231) cell line, among the nine screened compounds, 3d, 3c, 3g, and 3a exhibited moderate to good antiproliferative activity with IC₅₀ values in the range 14.06–8.03 µM concentration. The compound 3d exhibited higher activity with IC₅₀ value 8.03 µg/mL, compared to 3c with IC₅₀ value of 12.03 µg/mL. Whereas, compounds 3g, 3b, 3h, 3a, and 3i also exhibited significant cytotoxicity with IC₅₀ values in the range 05.18–18.17 µM concentration. Further, the compound 3g exhibited distinct activity with IC₅₀ value 05.18 µg/mL, followed by compound 3b with IC₅₀value of 09.09 µg/mL for A-549 cancer cell line. However, for HT29 cell line all of the compounds showed significantly lesser activity when compared with standard drug Cisplatin. In addition, the synthesized compounds were screened for their anti-TB activity and its cytotoxicity, the compound 3g exhibited excellent antitubercular activity with MIC of 0.78 µg/mL, while the compound 3b exhibiting MIC of 1.56 µg/mL with the highest safety percentage survival of 72% and 78%.

Keywords:

• Anti-TB activity
• antiproliferative activity
• molecular docking

Acknowledgments

The authors are very much thankful to Department of Chemistry, Karnataka University’s Karnataka Science College, Dharwad, for providing necessary Research facilities. The authors acknowledge Karnatak University’s ‘University Scientific Instrument Center’ for technical support for this research work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Smita G. Mane and Dr. Kariyappa S. Katagi highly acknowledges to UGC New Delhi, India for providing Rajiv Gandhi National Fellowship (RGNF) (F117.1/2016-17/RGNF-2015-17-SC-MAH-26074/(SAIII/Website) and UGC-SWRO, Bangalore for granting research project no. F.2070-MRP/15-16/KAKA056/UGC-SWRO, respectively.