Synthesis, vibrational analysis, molecular property investigation, and molecular docking of new benzenesulphonamide-based carboxamide derivatives against Plasmodium falciparum

• Published in: Journal of molecular structure 2022-12, Vol.1269, p.133796, Article 133796
• Main Authors: Izuchukwu, Ugwu D., Asogwa, Fredrick C., Louis, Hitler, Uchenna, Eze F., Gber, Terkumbur E., Chinasa, Ugwu M., Chinedum, Ndefo J., Eze, Benedeth O., Adeyinka, Adedapo S., Chris, Okoro U.
• Format: Article
• Language: English
• Subjects: Carboxamide; DFT; Molecular docking; Plasmodium falciparum; Synthesis
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133796

•Four new derivatives of carboxamides containing sulphonamide functionality have been synthesized using zinc chloride as a catalyst.•The energy gap was comparably same although the reactivity was seemed to be in the trend 4.7400 eV > 4.2559 eV > 4.0640 eV > 4.0580 eV.•the highest E(2) energies which results in the highest interaction within the studied molecules were observed to have five major transition which include π* → π*, π→π*, σ→ σ*, σ*→ σ* and LP→ σ*.•Experimental spectral absorption of strong intensity which correspond to the studied compound and agrees with theoretically calculated data.•the 2-[N-benzoylated]-alkane derivatives; [BSPFMNPB] and [BSPFMNPP] are better anti-malaria drug than their 1-[N-benzoylated]-pyrollidine derivatives; [BSNPPC] and [BSHNPPC]. Zinc chloride mediated synthesis, density functional theory (DFT) studies and molecular docking of new carboxamide derivatives containing sulphonamide functionality is reported. The synthesis of benzenesulphonamide (3a-d) was achieved from the reaction of benzenesulphonyl chlorides (1a) and amino acids (2a-d) and the yields were characterized using FT-IR and NMR spectroscopy. The reaction of compounds (3a-d) with benzoyl chloride (4) provided the N-benzoylated derivatives (5a-d) which upon reaction with 4-nitroaniline (6) using zinc chloride as a catalyst afforded the new carboxamides; 2-[N-(benzenesulfonyl)-1-phenylformamido]-3-methyl-N-(4-nitrophenyl)pentanamide (BSPFMNPP), 2-[N-(benzenesulfonyl)-1-phenylformamido]-3-methyl-N-(4-nitrophenyl)butanamide, (BSPFMNPB), 1-(benzenesulfonyl)-4-hydroxy-N-(4-nitrophenyl)pyrrolidine-2-carboxamide (BSHNPPC) and 1-(benzenesulfonyl)-N-(4-nitrophenyl)pyrrolidine-2-carboxamide (BSNPPC) in excellent yields. Theoretical calculations on the newly synthesized carboxamides were conducted at the B3LYP/6-311++G(d,p) level of theory to investigate the reactivity, stability, bonding nature, along with vibrational functional groups assignment and correlation with experimental values. From the docking result, the binding affinities obtained from the docking score were in the order; -7.3 > -7.2 > -6.1 > -5.8 kcal/mol for BSPFMNPB, BSPFMNPP, BSNPPC and BSHNPPC respectively while the standard drug, atovaquone scored -7.7 kcal/mol. There were no significant differences between the docking score by the standard drug and the studied compounds. However, results showed that the 2-[N-benzoylated]-alkane derivatives (pentanamide and butanamide); BSPFMNPB and BSPFMNPP are bett