Design, molecular docking, synthesis, and biological evaluation of pyrido pyrimidine and pyrazolo pyrimidines for cytotoxic activity.

Aim: The study aims to design 25 pyrimidine scaffolds, synthesize selective compounds based on molecular docking simulations, characterization by spectral methods and biological evaluation for cytotoxic activity. Materials and Methods: All the required chemicals were obtained from Sigma-Aldrich Chemicals and SD-Fine Chemicals and the solvents used in the synthesis were laboratory grade. All Fourier transform infrared (FT-IR) spectra were recorded on Thermo Nicolet Nexus 4700 FT-IR instrument KBr disc method, 1H nuclear magnetic resonance (NMR) spectrum was recorded on Advance 300 MHz Bruker UX-NMR and the samples were made dimethyl sulfoxide-d6 using tetramethylsilane as internal standard, and the mass spectrum was recorded with high-resolution mass spectra on Thermo Finnigan LCQ Ion Trap instrument and they were reported in m/z as molecular ion peak. Results and Discussion: Selective compounds were synthesized, characterized by spectral methods, and evaluated for in vitro cytotoxic potency against hepatocellular carcinoma (Hep G2), MCF-7, and HeLa cell lines. Conclusion: It is seen that all the synthesized compounds showed significant activity. Among all, the IC50 values of the compounds 9g, 13c, and 13e reported good activity against HeLa, MCF-7, and Hep G2 cell lines were found at 28.58, 12.79, and 37.59 μg/ml, respectively, as most potent compounds. Good agreement was observed between the top experimental inhibitors and top-ranked docking scores. Hence, the compounds could be considered as new anticancer hits for further lead optimization. [ABSTRACT FROM AUTHOR] Copyright of Drug Invention Today is the property of Journal of Pharmacy Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)