Synthesis and structural characterisation of bismuth(iii) hydroxamates and their activity against Helicobacter pylori

Abstract

Seven new bismuth(iii) hydroxamate complexes derived from the hydroxamic acids N-methylfurohydroxamic acid (H-MFHA), N-benzoyl-N-phenylhydroxamic acid (H-BPHA), salicylhydroxamic acid (H2-SHA), benzohydroxamic acid (H2-BHA), and acetohydroxamic acid (H2-AHA) have been synthesized and characterized. The complexes formed are either tris-hydroxamato complexes containing only mono-anionic ligands, [Bi(H-SHA)3], [Bi(MFHA)3] and [Bi(BPHA)3]; mixed-anion complexes, [Bi(SHA)(H-SHA)] and [Bi(AHA)(H-AHA)]; and potassium bismuthate complexes, K[Bi(SHA)2] and K[Bi(BHA)2]. The solid-state structure of three complexes has been determined through single crystal X-ray diffraction; [Bi(MFHA)3]2·Me2C[double bond, length as m-dash]O, {[Bi(SHA)(H-SHA)(DMSO)2][Bi(SHA)(H-SHA)(DMSO)]·DMSO}∞ and [Bi(BPHA)3]2·2EtOH. All the complexes and their parent acids were assessed for the bactericidal activity against three strains of Helicobacter pylori (26695, B128 and 251). Of the acids, only acetohydroxamic acid showed any activity at low concentrations (MIC 6.25 μg mL(-1); 83.26 μM) while the others were not toxic below 25 μg mL(-1). In contrast, their bismuth(iii) complexes all showed excellent activity across all three strains (e.g. 0.28 μM for [Bi(H-SHA)3] to 6.01 μM for K[Bi(BHA)2] against strain 251) with only minor variations in activity being both ligand and composition dependant.

Bismuth Phosphinates in Bi‐Nanocellulose Composites and their Efficacy towards Multi‐Drug Resistant Bacteria

“…[41] However,m any bismuth complexes also exhibit good antibacterial activity, [40,[42][43][44][45] including bismuth carboxylates (used to treat Helicobacter pylori (H. pylori)i nfection), and certain "bismuth thiol" complexes which are known to inhibitb iofilm formation. [40,45] Our recent studies have shown that bismuth complexes of arene-sulfonates, amino-arene sulfonates and hydroxamates [46][47][48] act against H. pylori in low mm-high nm concentrations, which is orders of magnitudeb etter than current carboxylate based medications, while bismuth(III) thiolates derived from small heterocyclic thiones display remarkable broad-spectrum antibacterial activity (including against MRSA and VRE) at low mm concentrations. [49][50][51][52] Organophosphorus compounds, in particularp hosphinic acids (R 1 R 2 P(=O)OH), are known to have antibacterialp roperties.…”

Biomedicinal and Gastroprotective Aspects of Organobismuth Compounds: Recent Approaches and Future Perspectives

“…They also reported that benzohydroxamates were potentially more effective than the other complexes studied until now. Hence, further investigation of these complexes is required, and in same context novel bismuth (III) hydroxamates derived from N-methylfurohydroxamic acid (H-MFHA), N-benzoyl-Nphenylhydroxamic acid (H-BPHA), salicylhydroxamic acid (H2-SHA), and acetohydroxamic acid (H2-AHA) were also synthesized [102].…”

Exposure and nephrotoxicity concern of bismuth with the occurrence of autophagy

“…The mechanisms for bacteria removal are unclear, although competition for ferric ions and interaction with regulatory proteins have been proposed (Li and Sun, 2012; Sun and Szeto, 2003). In addition, some novel Bi compounds such as hydroxamate benzohydroxamate derivatives have been synthesized, showing excellent antimicrobial activities (Pathak et al, 2014, 2015). The major drawback of Bi therapy is its toxicity when digested, but the development of new drugs through the combination of Bi with polysaccharides has shown greater activities with minimum adverse effects (Zhu et al, 2014).…”