Ravi Kumar Mittal and Priyank Purohit* Pages 1708 - 1716 ( 9 )
Background: The 2-styrylquinoline-3-carboxylate derivatives have been reported as antiproliferative agents.Objective: The aim of the study was to enhance the selectivity of the drug to the cancer cells. The change in pKa value can be the boost point to enhance the selectivity. The selectivity of the drug will enhance concentration in the cancer cells and will reduce the absorption in the non-cancerous cells. Methods: The designed hydrolysis of the ester group was obtained through the reported method to change the physiological properties, which was correlated with the in-silico and in-vitro selectivity studies. The compounds were characterized through important analytical techniques, moreover, the biological results of all compounds were obtained through in-vitro cancer (MCF-7 and K562) and non-cancerous (HFK293) cell line. Results: The synthesized compounds exhibited micromolar inhibition with a higher selectivity than their ester parent compounds, however, the compound showed better activity to the cancer cell, because of the minimal distribution of the drug in the non-cancerous cells. The compound 2f and 2l were found more selective and potent. Conclusion: The designed 2, 4-disubstituted quinoline-3-carboxylic acid derivatives were evaluated in in-vitro cancer (MCF-7 and K562) and non-cancerous (HEK293) cell lines. The most concern issue was resolved by changing the pKa value of compounds, which was calculated by the software base study. The selectivity was correlated with the previously reported ester molecules. The synthesized compounds were characterized by important analytical techniques. The unionized/nonpolar form in the acidic cancer tissue environment, which enhances the drug absorption ion in an acidic medium, was also proved through the in-vitro results; hence the compound showed better activity to the cancer cells because of the minimal distribution of the drug in the noncancerous cells. The more selective or less toxic anti-cancer compounds 2f and 2l were reported with all relevant experimental results as in-silico quantitative estimation of drug-likeness (QED) and absorption, distribution, metabolism, excretion, and toxicity (ADMET).
Cancer, anti-cancer, selectivity, anti-cancer drug, weak acidic drug, absorption of drug.
Department of Natural Product, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar, Punjab-160062, Department of Pharmacy, HIMT, Gautam Budha Nagar, Greater Noida, Uttar Pradesh, 201308