Computational techniques for analyzing and interpreting some quinoxaline-containing molecules as possible anti-schistosomal agents using docking, pharmacokinetics, drug-likeness, QSAR, and molecular dynamics evaluation

Abstract

Schistosomiasis, a parasitic disease caused by Schistosoma species, remains a significant public health concern in tropical and subtropical areas, affecting over 240 million humans globally. The existing cure possibilities for schistosomiasis are inadequate, and the emergence of resistance to the widely used antischistosomal drug, praziquantel, has led to the finding and improvement of novel therapeutic agents. This research outlines a comprehensive approach that helped identify and investigate the quinoxaline core as a potential anti-schistosomal scaffold. These were done using computational concepts to search PubChem data, and compound 20 with a PubChem CID of 155459055 with a quinoxaline core was discovered and further modified. The modified compounds (MCs) were assumed to be more biologically active than the template molecule (TM) and reference compound (RC), as MCs show predicted biological activities (pIC50) in the range of 9.570 to 10.72 against the TM, with pIC50 of 8.251 and 8.321 for the RC, respectively. Furthermore, they have a higher negative ∆G in the range of 31.07–44.98 kcal/mol when compared to the praziquantel with a ∆G of -30.82 kcal/mol, indicating more stability. The ADMET study further validated these MCs' improved therapeutic properties. The findings imply that the identified compounds are potential anti-schistosomal drugs that require additional research due to their remarkable efficacy and selectivity. Further validation with MD simulation confirmed the stability of the DC4, which could be a much-needed substitute for praziquantel in aiding schistosomiasis elimination tactics.