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

Abstract

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.

SHIP: identifying antimicrobial resistance gene transfer between plasmids

“…This complex integron has a sul1 gene, conferring sulfonamide resistance ( Antunes et al 2005 ). Despite widespread resistance, sulfonamides are widely used for treating urinary tract infections (UTI), wound healing, and in other clinical applications ( Swain et al 2021 ). The integron also harbors a qacE 1 gene, which confers resistance to disinfecting agents and antiseptics ( Kazama et al 1999 ).…”

Potential of Marine Terpenoids against SARS-CoV-2: An In Silico Drug Development Approach

“…Interestingly this study confirms that selected terpenoids exhibits antiviral activity in lower concentrations while delivers no toxicity even after 10-fold concentration. On the other hand, several alternative techniques such as structural modification, chemical conjugation, nano-drug delivery, and polymer-coated formulations with tools of medicinal chemistry are available to improve the drug-ability profiles of most potential candidates [ 95 , 105 , 106 ].Overall, the above computational investigations with various bioinformatic, chemoinformatic tools and perspective drug analysis by SAR can analyze the potency, drug chemistry, and drug−ability to select potential ‘lead’ candidates from a plethora of broad-spectrum antiviral marine terpenoids, i.e., brevione F, stachyflin, and xiamycin systematically and cost−effectively to counter the newly emerged SARS-CoV-2.…”

Piperlongumine and its derivatives against cancer: A recent update and future prospective

“…[39] Therefore, chemical modification or chemical hybridization is an ideal platform through combinatorial chemistry, click chemistry and medicinal chemistry protocols for the synthesis of potent natural-based semisynthetic drug candidates. [40][41][42][43][44][45][46][47][48]…”