A Novel Antimicrobial–Phytochemical Conjugate With Antimicrobial Activity Against Streptococcus uberis, Enterococcus faecium, and Enterococcus faecalis

Abstract

Antimicrobial resistance is one of the major threats to human and animal health. An effective strategy to reduce and/or delay antimicrobial resistance is to use combination therapies. Research in our laboratory has been focused on combination therapies of antimicrobials and phytochemicals and development of antimicrobial–phytochemical conjugates. In this study, we report the synthesis and antimicrobial activity of a novel sulfamethoxazole–gallic acid conjugate compound (Hybrid 1). Hybrid 1 not only showed much stronger activity than sulfamethoxazole towards Streptococcus uberis 19436, Enterococcus faecium 700221, and Enterococcus faecalis 29212, which were purchased from American Type Culture Collection (ATCC), but also exhibited a promising antimicrobial effect against two E. faecalis clinical isolates, one of which was multidrug-resistant. Further studies are warranted to establish the in vivo antimicrobial activity for Hybrid 1 and develop more potent sulfamethoxazole–gallic acid-based antimicrobial conjugates using hybrid 1 as a lead compound.

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

“…Overall, in most cases, phytochemical bearing derivatives displayed lesser toxicity than synthetic products (Swain, Paidesetty, Padhy, & Hussain, 2020), and the current report also suggests that the development of sulfonamides–phytochemical conjugates may be a promising strategy in tackling MDR‐bacteria (Irfan, Rubab, Rehman, et al, 2020; Rajamanickam et al, 2019; Swain, Paidesetty, & Padhy, 2020).…”

“…A novel SMZ‐gallic acid hybrid followed by a multistep synthesis procedure was proposed (Rajamanickam, Yang, & Sakharkar, 2019). The combination exhibited significant antibacterial activity than individual SMZ and potent against clinically isolated MDR‐ Enterococcus faecalis , E .…”

“…The combination exhibited significant antibacterial activity than individual SMZ and potent against clinically isolated MDR‐ Enterococcus faecalis , E . faecium , and Streptococcus uberis (Rajamanickam et al, 2019). Blithely, several natural products/natural pharmacophores containing conjugates such as, sulfonamide‐indole‐3‐carboxaldehyde (Chohan, Youssoufi, Jarrahpour, Ben, & Hadda, 2010), benzene sulfonic acid‐1‐methyl hydrazine derivatives were synthesized (Aslan, Ozcan, & Karacan, 2012), salicylanilide 4‐(trifluoromethyl)benzoates (Krátký, Vinšová, et al, 2013), sulfonamide derivatives of chlorosulfonyl isocyanate conjugated products (Boufas, Dupont, Berredjem, et al, 2014), N‐acylated derivatives of SMZ and sulfafurazole (Marwaha, Uvell, Salin, et al, 2014), a series of SMZ‐based n ‐alkyl ureas (Krátký et al, 2017), and sulfonamide‐heterocyclic products (Naaz, Srivastava, Singh, et al, 2018) had been synthesized and reported having potential antibacterial, antifungal and antimycobacterial activities.…”