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Staphylococcus aureus, a notorious member of the ESKAPE pathogens, poses significant public health challenges due to its virulence and multidrug-resistant nature, particularly in methicillin-resistant S. aureus (MRSA) strains. With the increasing threat of antibiotic resistance, there is an urgent need to develop novel antibiotic agents. This study therefore aims to explore the antibacterial potential of 1,2-dibenzoylhydrazine (DBH) as a scaffold against S. aureus drug target enzymes, using integrated computational approaches. The study utilized molecular docking, lead optimization, and structure-based virtual screening techniques to evaluate the binding affinities of DBH and its derivatives against various S. aureus enzymes. Prime/MM-GBSA calculations were performed to validate the binding affinities obtained, and molecular dynamics (MD) simulations were conducted to assess the stability of the DBHs-enzyme complexes. Results indicated that, out of twenty enzymes from S. aureus examined against DBH, carotenoid dehydrosqualene synthase was predicted as a suitable target enzyme for DBH, showing a binding affinity of -8.027 kcal/mol. A lead optimization operation of the compound generated 27 DBH derivatives out of which four exhibited enhanced binding affinities compared to both DBH and a standard antibiotic, ofloxacin. The QSAR model predicted that, DBH and molecule_D_1 have higher PIC50 of 4.779 µM compared with the standard drug (ofloxacin = 4.678 µM). MD simulations confirmed the stability of the top-scoring derivatives within the enzyme's binding pocket, with RMSD and RMSF analyses supporting their potential as inhibitors of the enzyme. In conclusion, this study has predicted the effect of DBH derivatives on S. aureus based on their in silico inhibitory capacity against the carotenoid dehydrosqualene synthase from the organism. Future work will seek to experimentally validate these findings against the suggested enzyme. [ABSTRACT FROM AUTHOR]

Azabenzimidazoles are among the substrates most frequently found in small-molecule drugs due to their broad-spectrum biological activity. Newer drugs are continually in need of to replace existing drugs which encounter microorganism drug resistance. The reaction of 2,3-diaminopyridine precursors with variously substituted benzaldehydes has provided convenient and efficient access to a series of 4-azabenzimidazole derivatives and, regioselectively, to a series of 2-amino-5-bromo-3-(phenylimino)pyridine derivatives, while sodium cyanoborohydride reduction of the latter has afforded the corresponding 2-amino-5-bromo-3- (phenylamino)pyridine analogues. Bioassays of these and other compounds have been undertaken to explore their cytotoxicity and their activity against the parasitic protozoans, Plasmodium falciparum and Trypanosoma brucei. A number of the compounds show promising selective activity against T. brucei with IC50 values as low as 1.3 µM while two of them exhibit encouraging activity against both T. brucei and P. falciparum. [ABSTRACT FROM AUTHOR]

A small library of nine, novel 2,4-diarylquinoline derivatives has been prepared in high yield via convenient one- or two-step routes from a series of substituted 2-aminobenzophenones. None of the products exhibited toxicity at 20 μM against human cervix adenocarcinoma (HeLa) cells, while many of them exhibited encouraging trypanocidal activity against T. brucei brucei (a parasite responsible for African cattle trypanosomiasis) - some with IC50 values in the range 2.8 - 6.2 μM. [ABSTRACT FROM AUTHOR]

• Synthesis of 5-bromo-1-[(N -substututed-carbamoyl)methyl]-7-azabenzimidazoles. • DNMR and theoretical analyses of amide rotamerism. • Evaluation of cytotoxocity and activity against P.falciparum and T.Brucei. The Cs 2 CO 3 -catalysed condensation of 5-bromo-7-azabenzimidazole with a series of bromomethyl ketones has afforded a small library of ten, novel 5-bromo-1-[(N -substututed-carbamoyl)methyl]-7-azabenzimidazoles. Rotamerism in the products, as evidenced by the splitting of 1H- and 13C-NMR signals, is attributed to hindered internal rotation about the amide N-C(=O) bond, and has been explored using dynamic NMR (DNMR) analysis and computational methods at the GIAO B3LYP/6-311+G(2d,p) level of theory. Coalescence temperatures have been obtained for representative examples and rotational barriers determined experimentally and theoretically. A detailed theoretical analysis has been undertaken to explore conformations which may contribute to the relative populations of the s-cis and s-trans rotamers. The products have also been screened for cytotoxicity and activity against two parasitic protozoan strains (Plasmodium falciparum and Trypanosoma brucei). [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Herein a pH-adjusted chemical precipitation method is reported for in-situ formation of ternary Ag 2 O-Ag 2 CO 3 /g-C 3 N 4 (AAG) composites in the presence of atmospheric CO 2. For comparison, a Janus Ag 2 O-Ag 2 CO 3 (AA) composite with fine and narrow size particles of high purity was also fabricated with AgNO 3 and NaOH without g-C 3 N 4 (GN). The thermal treatment of the AAG composite by TGA indicates that 14% of atmospheric CO 2 was utilized by Ag 2 O which induced the formation of ternary AAG. The thermal stability of the prepared samples is in the order of GN > AAG > AA. Results from other spectroscopic techniques on AAG affirmed that both Ag 2 O and Ag 2 CO 3 co-existed on the surface of g-C 3 N 4. Under solar illumination, the constituting particles of AAG realigned at their interfaces to form p-n/n-n dual heterojunctions with improved photocatalytic reduction of nitrophenols (4 and 2-nitrophenols) to aminophenols (4 and 2-aminophenols), and Cr(VI) to Cr(III). The results obtained from this study showed that AAG has higher photoreduction efficiencies compared to AA and GN. The results from the stability runs also showed that AAG has good photo-stability and reusability to catalyze the reduction of nitrophenols and hexavalent chromium under light irradiation with efficiency as high as 89% for five (5) reaction cycles. This study further highlights the significance of Ag 2 O utilizing CO 2 to promote Ag 2 O/Ag 2 CO 3 formation as a co-catalyst for photocatalytic applications. [ABSTRACT FROM AUTHOR]