Novel sulfonamide derivatives as a tool to combat methicillin-resistant Staphylococcus aureus.

Increasing resistance in Staphylococcus aureus has created a critical need for new drugs, especially those effective against methicillin-resistant strains (methicillin-resistant Staphylococcus aureus [MRSA]). Sulfonamides are a privileged scaffold for the development of novel antistaphylococcal agents. This review covers recent advances in sulfonamides active against MRSA. Based on the substitution patterns of sulfonamide moieties, its derivatives can be tuned for desired properties and biological activity. Contrary to the traditional view, not only N-monosubstituted 4-aminobenzenesulfonamides are effective. Novel sulfonamides have various mechanisms of action, not only 'classical' inhibition of the folate biosynthetic pathway. Some of them can overcome resistance to classical sulfa drugs and cotrimoxazole, are bactericidal and active in vivo. Hybrid compounds with distinct bioactive scaffolds are particularly advantageous.

Synthesis, characterization of novel N-(4-cyano-1,3-oxazol-5-yl)sulfonamide derivatives and in†vitro screening their activity against NCI-60 cancer cell lines.

A novel series of N-(4-cyano-1,3-oxazol-5-yl)sulfonamides have been synthesized and characterized by IR, 1 H NMR, 13 C NMR spectroscopy, elemental analysis and chromato-mass-spectrometry. The anticancer activities of all newly synthesized compounds were evaluated via a single high-dose assay (10 µM) against 60 cancer cell lines by the National Cancer Institute (USA) according to its screening protocol. Among them, compounds 2 and 10 exhibited the highest activity against the 60 cancer cell lines panel in the one-dose assay. Compounds 2 and 10 showed inhibitory activity within the GI50 parameter and in five dose analyses. However, their cytostatic activity was only observed against some cancer cell lines, and cytotoxic concentration was outside the maximum used, i. e., >100 µM. The COMPARE analysis showed that the average graphs of the tested compounds have a moderate positive correlation with compounds with the L-cysteine analog and vinblastine (GI50 ) as well as paclitaxel (TGI), which target microtubules. Therefore, disruption of microtubule formation may be one of the mechanisms of the anticancer activity of the tested compounds, especially since among tubulin inhibitors with antitumor activity, compounds with an oxazole motif are widely represented. Therefore, N-(4-cyano-1,3-oxazol-5-yl)sulfonamides may be promising for further functionalization to obtain more active compounds.

Selective Bacterial Growth Inactivation by pH-Sensitive Sulfanilamide Functionalized Carbon Dots.

Carbon dots (CDs) were synthesized hydrothermally by mixing citric acid (CA) and an antifolic agent, sulfanilamide (SNM), employed for pH sensing and bacterial growth inactivation. Sulfanilamide is a prodrug; aromatic hetero cyclization of the amine moiety along with other chemical modifications produces an active pharmacological compound (chloromycetin and miconazole), mostly administered for the treatment of various microbial infections. On the other hand, the efficacy of the sulfanilamide molecule as a drug for antimicrobial activity was very low. We anticipated that the binding of the sulfanilamide molecule on the carbon dot (CD) surface may form antibacterial CDs. Citric acid was hybridized with sulfanilamide during the hydrothermal preparation of the CDs. The molecular fragments of bioactivated sulfanilamide molecule play a crucial role in bacterial growth inactivation for Gram-positive and Gram-negative bacteria. The functional groups of citric acid and sulfanilamide were conserved during the CD formation, facilitating the zwitterionic behavior of CDs associated with its photophysical activity. At low concentrations of CDs, the antibacterial activity was apparent for Gram-positive bacteria only. This Gram-positive bacteria selectivity was also rationalized by zeta potential measurement.