Synthesis, crystal structure and in-silico evaluation of arylsulfonamide Schiff bases for potential activity against colon cancer.

Autor: Kolade SO; Department of Chemistry, University of Lagos, Akoka-Yaba, Lagos, Nigeria., Aina OS; Department of Chemistry, University of Lagos, Akoka-Yaba, Lagos, Nigeria., Gordon AT; Department of Chemistry, Nelson Mandela University, Port Elizabeth 6031, South Africa., Hosten EC; Department of Chemistry, Nelson Mandela University, Port Elizabeth 6031, South Africa., Olasupo IA; Department of Chemistry, University of Lagos, Akoka-Yaba, Lagos, Nigeria., Ogunlaja AS; Department of Chemistry, Nelson Mandela University, Port Elizabeth 6031, South Africa., Asekun OT; Department of Chemistry, University of Lagos, Akoka-Yaba, Lagos, Nigeria., Familoni OB; Department of Chemistry, University of Lagos, Akoka-Yaba, Lagos, Nigeria.
Jazyk: angličtina
Zdroj: Acta crystallographica. Section C, Structural chemistry [Acta Crystallogr C Struct Chem] 2024 Apr 01; Vol. 80 (Pt 4), pp. 129-142. Date of Electronic Publication: 2024 Mar 28.
DOI: 10.1107/S205322962400233X
Abstrakt: This report presents a comprehensive investigation into the synthesis and characterization of Schiff base compounds derived from benzenesulfonamide. The synthesis process, involved the reaction between N-cycloamino-2-sulfanilamide and various substituted o-salicylaldehydes, resulted in a set of compounds that were subjected to rigorous characterization using advanced spectral techniques, including 1 H NMR, 13 C NMR and FT-IR spectroscopy, and single-crystal X-ray diffraction. Furthermore, an in-depth assessment of the synthesized compounds was conducted through Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis, in conjunction with docking studies, to elucidate their pharmacokinetic profiles and potential. Impressively, the ADMET analysis showcased encouraging drug-likeness properties of the newly synthesized Schiff bases. These computational findings were substantiated by molecular properties derived from density functional theory (DFT) calculations using the B3LYP/6-31G* method within the Jaguar Module of Schrödinger 2023-2 from Maestro (Schrodinger LLC, New York, USA). The exploration of frontier molecular orbitals (HOMO and LUMO) enabled the computation of global reactivity descriptors (GRDs), encompassing charge separation (E gap ) and global softness (S). Notably, within this analysis, one Schiff base, namely, 4-bromo-2-{N-[2-(pyrrolidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 20, emerged with the smallest charge separation (ΔE gap  = 3.5780 eV), signifying heightened potential for biological properties. Conversely, 4-bromo-2-{N-[2-(piperidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 17, exhibited the largest charge separation (ΔE gap  = 4.9242 eV), implying a relatively lower propensity for biological activity. Moreover, the synthesized Schiff bases displayed remarkeable inhibition of tankyrase poly(ADP-ribose) polymerase enzymes, integral in colon cancer, surpassing the efficacy of a standard drug used for the same purpose. Additionally, their bioavailability scores aligned closely with established medications such as trifluridine and 5-fluorouracil. The exploration of molecular electrostatic potential through colour mapping delved into the electronic behaviour and reactivity tendencies intrinsic to this diverse range of molecules.
(open access.)
Databáze: MEDLINE
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