Phytochemical conjugation as a potential semisynthetic approach toward reactive and reuse of obsolete sulfonamides against pathogenic bacteria.

The emergence and reemergence of multidrug-resistant (MDR) bacteria and mycobacteria in community and hospital periphery have directly enhanced the hospitalization costs, morbidity and mortality, globally. The appearance of MDR pathogens, the currently used antibiotics, remains insufficient, and the development of potent antibacterial(s) is merely slow. Thus, the development of active antibacterials is the call of the day. The sulfonamides class of antibacterials was the most successful synthesized drug in the 19th century. Mechanically, sulfonamides were targeting bacterial folic acid biosynthesis and today, those are obsolete or clinically inactive. Nevertheless, the magic sulfonamide pharmacophore has been used continuously in several mainstream antibacterial, antidiabetic, antiviral drugs. Concomitantly, thousands of phytochemicals with antimicrobial potencies have been recorded and were commanded as alternate antibacterials toward control of MDR pathogens. However, none/very few isolated phytochemicals have gone up to the pure-drug stage due to the lack of the desired drug-likeness values and the required pharmacokinetic properties. Thus, chemical modification of parent drug remains as the versatile approach in antibacterial drug development. Improvement of clinically inactive sulfa drugs with suitable phytochemicals to develop active, low-toxic drug molecules followed by medicinal chemistry could be prudent. This review highlights such "sulfonamide-phytochemical" hybrid drug development research works for utilizing inactive sulfonamides and phytochemicals; the ingenious cost-effective and resource-saving hybrid drug concept could be a new trend in current antibacterial drug discovery to reactive the obsolete antibacterials.