Cedric Dzidzor Kodjo Amengor

Venom-derived antimicrobial peptides (AMPs) are promising scaffolds for next-generation antimicrobial agents because of their structural diversity and memb

Bicyclo[3.3.0]skeleton is a common structural motif present in many natural products and pharmaceutical agents. Here we have synthesized a rigid 3a-arylhexahydropentalene-1,6-dione from cyclopent-2-en-1-one which is an easy and readily available starting material.

Owing to their distinctive physicochemical features, their structural analogues of benzene ring bioisosteres, and their strong affinity for biomacromolecules, pyridine derivatives function both as core structural scaffolds in pharmacologically active compounds and as versatile elements for optimizing key drug-like properties, such as water solubility, membrane permeability, and metabolic stability. In this study, we synthesized five pyridine-fused heterocyclic compounds using common synthetic intermediates as precursors.

The rapid emergence of pan-drug-resistant pathogens necessitates innovative antimicrobial strategies that overcome conventional resistance. This study reports the structure-guided design of sulfamethoxazole derivatives as dual inhibitors of quorum sensing (LasR) and efflux pumps (AcrB), alongside the classic dihydropteroate synthase (DHPS) target. High-throughput virtual screening of 54 derivatives, followed by MM-GBSA analysis, prioritized five novel compounds for synthesis. Their structures were confirmed by ¹H/¹³C NMR, FT-IR, and mass spectrometry. All compounds demonstrated potent growth inhibition (MICs 15.625–125 µg mL⁻¹) against Proteus mirabilis, Salmonella typhi, and Escherichia coli, though activity against the more resistant Pseudomonas aeruginosa was reduced. Critically, lead compounds SMX033 and SMX015 achieved >99% biofilm inhibition against P. mirabilis, and SMX033 showed significant efflux pump inhibition, directly validating our in silico predictions of a multi-target mechanism. In particular, compound SMX033 exhibited the best antimicrobial activity and lowest cytotoxicity of all the sulfamethoxazole derivatives with a CCC₅₀ value of 286.20 µM against Vero cells. Despite their predicted in silico genotoxicity, these derivatives provide promising chemical scaffolds for combating multidrug-resistant infections by concurrently attenuating virulence and restoring antibiotic susceptibility.

Memecylon amoenum is traditionally employed across West Africa for treating waist pains, diarrhoea, wounds, toothache and various skin ailments. The study aimed to identify major phytoconstituents using standard phytochemical screening, chromatographic separation, and FTIR analysis and to evaluate the biological activities of the methanol and petroleum ether leaves extracts. Phytochemical investigations revealed twelve constituents in the pulverized plant material and eleven in the methanolic extract, while the petroleum ether extract contained six. In the DPPH assay, the methanol and petroleum ether extracts of M. amoenum demonstrated IC₅₀ values of 11.42 ± 0.05 and 43.42 ± 0.62 µg/mL, respectively, outperforming ascorbic acid (58.46 ± 0.8 µg/mL). Total antioxidant capacity values (gAAE/100 g) were 36.04 ± 1.43 for the hetmethanol extract and 31.35 ± 3.98 for the petroleum extract. The extracts also exhibited potent anthelmintic activity, surpassing mebendazole at all tested concentrations for example the death time at 6mg/mL are 2min 05s, 4min 16s and 8min 33s respectively for the methanol extract, pet-ether extract and mebendazole. Both extracts showed broad antimicrobial effects, with minimum inhibition concentrations, 0.0122 to 25 mg/mL, and demonstrated notable anti-inflammatory properties. Thin-layer chromatographic profiling revealed four spots in the methanolic extract and seven in the petroleum ether extract, suggesting chemical diversity between the solvent fractions. FTIR spectra confirmed the presence of functional groups consistent with the compounds detected through phytochemical screening. The results indicate that the methanol and petroleum ether extracts of M. amoenum possess significant antioxidant, anti-inflammatory, antimicrobial and anthelmintic activities, supporting their potential as therapeutic effect.

A series of 2,3‐dihydrobenzo[b][1,4]thiazepine derivatives have been synthesized and characterized using IR, NMR, GC‐MS and microanalysis. The compounds were found to exhibit variable activity against Escherichia coli , Klebsiella pneumoniae , Enterococcus faecalis and Salmonella typhi with MIC values ranging from 1.88–15 mg/mL. The best activity was observed in compounds 4 and 6 with MIC of 1.875 mg/mL against E . faecalis. Compound 6 was also the most active against S . aureus with MIC of 1.875 mg/mL. The in silico computational docking revealed that the compounds have excellent binding to both multiple targets of E. coli and Staphylococcus aureus dihydrofolate reductase enzymes (PDB ID: 6XG5 and 6P9Z) and good binding to the S. aureus dihydropteroate synthase enzyme (PDB ID: 1ad4). The computational pharmacokinetic study showed that the highly orally bioavailable compounds were not P‐gp (p‐glycoprotein substrate). The compounds were found to be excellent hERG blockers.

The present study investigated the antifungal activity of the 70% ethanol extracts of the leaves (IGL), stem bark (IGSB) and roots (IGR) of Irvingia gabonensis against multidrug‐resistant Candida albicans and Candida glabrata strains and clinical isolates. The inhibitory activities of extracts against biofilm formation and mature biofilms were also investigated. Furthermore, the effects of the combinations of I. gabonensis extracts with amphotericin B, ketoconazole, voriconazole, nystatin and caspofungin, against the resistant Candida strains and isolates were evaluated using the checkerboard assay. Qualitative and quantitative assessments of the phytoconstituents in the plant extracts, as well as their antioxidant activities, were then analysed. IGSB displayed considerable anti‐ Candida activity with minimum inhibition concentrations (MICs) of 15.63 μg/mL–500 μg/mL, while IGR showed MICs of 125 μg/mL–1000 μg/mL. IGL demonstrated limited activity with MICs of 500 μg/mL–> 2000 μg/mL. IGSB also exerted significant antibiofilm activity against the drug‐resistant C . albicans and C . glabrata strains and isolates with SMIC ₉₀ of 31.25 μg/mL–1000 μg/mL and 125 μg/mL–2000 μg/mL against the formation of biofilms and mature biofilms, respectively. In the checkerboard assay, IGSB recorded the most synergistic interactions with the conventional antifungal drugs producing median FICI values that ranged between 0.35 to 0.61 and 0.30 to 0.68, and synergistic action that ranged between 50% to 66.67% and 55.56% to 100%, against the MDR C. albicans and C. glabrata isolates, respectively. The extracts displayed strong antioxidant activities, which correlated with their total phenol, flavonoid and tannin contents. The presence of phytochemicals such as glycosides, coumarins and triterpenoids was also detected in I. gabonensis extracts. The study findings have demonstrated that I. gabonensis , particularly its stem bark, is a potential source of bioactive compounds that could be developed into novel antifungal agents.

Structural optimization integrating triphenylamine and quaternary ammonium salt-based antimicrobial peptide mimics has yielded novel theranostic hybrid molecules. These compounds exhibit fluorescence imaging, photodynamic antibacterial activity, and membrane-disruption capabilities, demonstrating broad-spectrum efficacy with low resistance induction. In this study, we successfully developed a novel triphenylamine-quaternary ammonium derivative (TPQ), ultimately obtaining the target compound (E)-8-(4-(4-(diphenylamino)styryl)phenoxy)-N,N,N-trimethyloctan-1-aminium bromide (Compound 5). This achievement provides a potent strategy against growing bacterial drug resistance.

Triphenylamine and phenol derivatives are two types of antimicrobial molecules with broad application prospects. Through functional modification, these compounds integrate fluorescence imaging and photodynamic antibacterial therapy, thereby achieving theranostic capabilities. They exert broad-spectrum and highly efficient antimicrobial activity via a membrane-disrupting mechanism, which consequently reduces the propensity for inducing drug resistance. In this work, triphenylamine-phenol derivatives (TPO) were designed and synthesized through three consecutive reactions: Wittig reaction, Heck reaction, and substitution reaction. Double bonds, hydroxyl groups, and brominated alkyl chains were gradually introduced to finally obtain the target product (E)-4-(4-((8-bromooctyl)oxy)styryl)-N,N-diphenylaniline (5). This study provides new insights into the development of novel and highly efficient antibacterial agents.