Synthesis and biological evaluation of aryl derivatives of isoxazole pyrazolo[1,5-a] pyrimidines as anticancer agents

ABSTRACT:

A new library of different substituted aryl derivatives of isoxazole-pyrazolo[1,5-a]pyrimidine (10a–j) were prepared, confirmed their structures by ¹HNMR, ¹³CNMR and mass spectral data. Furthermore, the preliminary anticancer activities of newly developed compounds (10a–j) were tested against four human cancer cell lines PC3 (prostate), DU-145 (Prostate), A549 (lung) and MCF-7 (breast) by utilizing of MTT method. The obtained results of were compared with standard reference etoposide. Among all, compounds (10a, 10b, 10c, 10e, 10i and 10j) displayed highest anticancer activities than standard. Predominantly, one compound 10a with 3,4,5-trimethoxy substituent on the aryl ring showed excellent activity. The molecular modeling studies indicated the interactions of synthesized compounds with SARM, and DNA via hydrogen bonds and hydrophobic interactions.

Graphical Abstract

Keywords:

• Zaleplon
• pyrazolo [1,5-a]pyrimidine
• oxaprozine
• 1,3-isoxazole and anticancer

Acknowledgments

The authors are thankful to KoneruLakshmaiah Education Foundationfor constant encouragement during this research program and thanks to Laurus Labs Limited, Hyderabad for providing basic research facility.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are also grateful to the Deanship of Scientific Research, King Khalid University for the financial support [Grant No. GRP/116/43].