Synthesis of azepane-acridine heterocyclic adducts assisted by the catalytic influence of γ-Fe2O3@TiO2-Vitamin B1 and evaluation of their medicinal potential through in vitro antimicrobial, QSAR, and molecular docking studies

Abstract

Present work elicits synthesis of novel azepane-acridines, assisted by titania-encapsulated γFe2O3 nanoparticles supported on Vitamin B1 (γFe2O3@TiO2-Vitamin B1) as a new magnetically recyclable heterogeneous nano-catalytic system. The reaction was accomplished using biocompatible PEG-200 (Polyethylene glycol) as the solvent under ultrasonic irradiations. The structure and morphology of synthesized magnetic nano-catalyst was ascertained based on data obtained from powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDAX), Fourier transform infrared (FT-IR), and VSM (Vibrating-sample magnetometer) TGA, DTA and DTG techniques. The characteristic size of the prepared heterogenous nano-catalyst is 34.62 nm. Also, the structures of all the synthesized azepane-acridine heterocyclic scaffolds were corroborated through spectro-analytical data. These new compounds were found to have remarkable biological activity profile against the bacterium S.aureus with IC50 values ranging from 1.41 to 2.75 µg/mL. Further, these in-vitro studies were correlated with statistically significant 2D/3D- QSAR models. The best 2D-QSAR models reveal the positive influence of slogp and Vander Waal Surface area descriptors while the negative influence of the polar surface area and T_2_N_6 descriptors on the bioactivity with ideal values of squared correlation coefficient (r2), cross-validated correlation coefficient (q2) with high values of Fisher ratio (F-test) indicating the model to be statistically relevant. The finest 3D-QSAR models MLR (Multiple Linear Regression method) provide practical information in the characterization and differentiation of compound binding sites. Moreover, molecular docking studies were performed to evaluate the antifungal activity of synthesized scaffolds against the black fungi crystal protein, indicating remarkable bioassay scores. Atom economy, practical feasibility, cost-effectiveness, minimum reaction time, High yields, and an additive-free process are the foremost advantages of the developed methodology.