Imidazopyridine chalcones as potent anticancer agents: Synthesis, single-crystal X-ray, docking, DFT and SAR studies
anticancer; docking; imidazopyridine; SAR studies; X-ray
New imidazopyridinechalcone analogs were synthesized through the ClaisenSchmidt condensation reaction. The newly synthesized imidazopyridine-chalcones (S1S12) were characterized using spectroscopic and elemental analysis. The structures of compounds S2 and S5 were confirmed by X-ray crystallography. The global chemical reactivity descriptor parameter was calculated using theoretically (DFT-B3LYP-3-211, G) estimated highest occupied molecular orbital and lowest unoccupied molecular orbital values and the results are discussed. Compounds S1S12 were screened on A-549 (lung carcinoma epithelial cells) and MDA-MB-231 (M.D. Anderson-Metastatic Breast 231) cancer cell lines. Compounds S6 and S12 displayed exceptional antiproliferative activity against lung A-549 cancer cells with IC50 values of 4.22 and 6.89 M, respectively, compared to the standard drug doxorubicin (IC50 = 3.79 ?M). In the case of the MDA-MB-231 cell line, S1 and S6 exhibited exceptionally superior antiproliferative activity with IC50 of 5.22 and 6.50 ?M, respectively, compared to doxorubicin (IC50 = 5.48 ?M). S1 was found to be more active than doxorubicin. Compounds S1S12 were tested for their cytotoxicity on human embryonic kidney 293 cells, which confirmed the nontoxic nature of the active compounds. Further molecular docking studies verified that compounds S1S12 have a higher docking score and interacted well with the target protein. The most active compound S1 interacted well with the target protein carbonic anhydrase II in complex with pyrimidine-based inhibitor, and S6 with human Topo II? ATPase/AMP-PNP. The results suggest that imidazopyridine-chalcone analogs may serve as new leads as anticancer agents. 2023 Deutsche Pharmazeutische Gesellschaft.
Soumyashree D.K.; Reddy D.S.; Nagarajaiah H.; Naik L.; Savanur H.M.; Shilpa C.D.; Sunitha Kumari M.; Shanavaz H.; Padmashali B.
ISSN: 3656233; PubMed ID: 37208792; CODEN: ARPMA
https://doi.org/10.1002/ardp.202300106 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159658186&doi=10.1002%2fardp.202300106&partnerID=40&md5=262869f749ab92f5ecb16f20f81edd62
Soumyashree D.K., Department of Chemistry, School of Basic Science, Rani Channamma University, Karnataka, Belagavi, India; Reddy D.S., Centre for Nano and Material Sciences, Jain (Deemed-to-be University), Jain Global Campus, Karnataka, Bangalore, India; Nagarajaiah H., Department of Chemistry, School of Applied Sciences, REVA University, Karnataka, Bangalore, India; Naik L., Department of Physics and Electronics, CHRIST University, Karnataka, Bangalore, India; Savanur H.M., Department of Chemistry, P. C. Jabin Science College, Karnataka, Hubballi, India; Shilpa C.D., Department of Chemistry, School of Applied Sciences, REVA University, Karnataka, Bangalore, India; Sunitha Kumari M., Department of Physics, Yuvaraja's College, University of Mysore, Karnataka, Mysuru, India; Shanavaz H., Department of Chemistry, Faculty of Engineering and Technology, Jain University, Jain Global Campus, Karnataka, Bangalore, India; Padmashali B., Department of Chemistry, School of Basic Science, Rani Channamma University, Karnataka, Belagavi, India