Toxigenic profiles of clinical Clostridioides difficile in public and private healthcare settings in Gauteng, South Africa

Results:The methylated 3-benzoylbenzofurans were discovered to be cytotoxic in TZM-bl cells, while the pyrazole derivatives showed mild to low cytotoxicity.The most active compounds included a non-methylated (2,5-dimethoxyphenyl)(5-hydroxy-4,7dimethyl-1-benzofuran-3-yl)methanone, a methylated benzofuran (2,5-dimethoxyphenyl)(5-methoxy-4,7-dimethyl-1-benzofuran-3-yl)methanone, and a pyrazole derivative (2-[3-(4-fluoro-2methoxyphenyl)-1H-pyrazol-4-yl]benzene-1,4-diol) with IC50 values that were comparable to nevirapine in both Q23 and CAP210 pseudoviruses.The cytotoxic benzofurans demonstrated high potency against cervical cancer and hepatic cancer cells and were also demonstrated to be potent antioxidants using a DPPH assay.Discussion: The current study successfully synthesized 3benzoylbenzofurans, methylated them, and finally prepared the pyrazole derivatives from the methylated 3-benzoylbenzofurans. Derivatization to pyrazole reduced the cytotoxicity of compounds as expected, fortunately maintaining their anti-HIV activities against pseudoviruses.Derivatives of pyrazoles increased the TPSA by 18.70 , which consequently lowed their cytotoxicity (Yukawa and Naven 2020).A flouro-pyrazole derivative was identified as the most potent inhibitor; although the mechanism has not been elucidated, it has the potential to inhibit the HIV capsid like lenacapavir (Segal-Maurer, DeJesus et al. 2022).The 3-benzoylbenzofurans demonstrated anticancer activities against a cervical cancer cell line and additionally displayed antioxidant activities.Conclusions: Together, these results demonstrate the potential of benzofurans and pyrazole derivatives for further development as antiretrovirals and anti-cancer treatment.