Schiff-based metal complexes of atenolol: Synthesis, characterization, molecular docking and biological evaluation

Background: The study also emphasizes the deployment of economical synthetic methods for obtaining more potent derivatives of commercially available drugs. Objective: The present study aimed to synthesize schiff-base (SB) derivatives of atenolol (ATN) and their metal complexes with copper and zinc; further characterized by various spectroscopic techniques as well as biological assay. Method: The synthesized compounds are subjected to in-silico docking and ADME (using Swiss ADME program) studies to confirm their suitability as lead molecule. Antioxidant, antimicrobial and anticancer activities were carried out using DDPH, disk diffusion method and MTT using HepG2 cell lines respectively. Additionally; Anti-hypertensive activity was tested L-NAME induced hypertensive rat model through invasive method. Results: Molecular docking studies indicate higher score for 4c and 5e than parent drug atenolol (ATN); SB and their metal derivatives also indicate promising therapeutic profile with good GIT absorption parameters. Here 4a represents potent antioxidant activity with IC50 = 8.95 ± 11?g/ml; when compared to std. drug Ascorbic acid with an IC50= 8.3± 11?g/ml. Furthermore; all the metal complexes are reactive against B.Subtilis a gram +ve bacteria than gram -ve E.Coli, 4a (39.31mm) and 4b (42.02mm) possessed higher antimicrobial activity when compared to std. drug Vancomycin (31.48mm). The results from MTT assay reveals higher anticancer potential (%age inhibition) of 4a (73%), 4d (75%) and 5d (74%) when compared to std. drug Doxorubicin (101.2%) at HepG2 cell lines. In-vitro analysis shows significant results with SB metal derivatives, where, Zn complexes of SB derivatives (5a-e) represents excellent anti-hypertensive activity in rats in contrast to standard drug alone. Conclusion: The imine Schiff based derivatives of atenolol and their metal complexes exhibit good biological efficacy as well as multi modal effects when compared to the frequently prescribed drug, atenolol.