Design, Synthesis, DFT, docking Studies, and antimicrobial evaluation of novel benzimidazole containing sulphonamide derivatives.

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.

Bridging fungal resistance and plant growth through constitutive overexpression of Thchit42 gene in Pelargonium graveolens.

KEY MESSAGE: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand.

In silico and network pharmacology analysis of fucosterol: a potent anticancer bioactive compound against HCC.

The Fucaceae family of marine brown algae includes Ascophyllum nodosum. Fucosterol (FSL) is a unique bioactive component that was identified through GC-MS analysis of the hydroalcoholic extract of A. nodosum. Fucosterol's mechanism of action towards hepatocellular cancer was clarified using network pharmacology and docking study techniques. The probable target gene of FSL has been predicted using the TargetNet and SwissTargetPred databases. GeneCards and the DisGNet database were used to check the targeted genes of FSL. By using the web programme Venny 2.1, the overlaps of FSL and HCC disease demonstrated that 18 genes (1.3%) were obtained as targeted genes Via the STRING database, a protein-protein interaction (PPI) network with 18 common target genes was constructed. With the aid of CytoNCA, hub genes were screened using the Cytoscape software, and the targets' hub genes were exported into the ShinyGo online tool for study of KEGG and gene ontology enrichment. Using the software AutoDock, a hub gene molecular docking study was performed. Ten genes, including AR, CYP19A1, ESR1, ESR2, TNF, PPARA, PPARG, HMGCR, SRC, and IGF1R, were obtained. The 10 targeted hubs docked with FSL successfully. The active components FSL of ASD, the FSL, are engaged in fatty liver disease, cancer pathways, and other signalling pathways, which could prove beneficial for the management of HCC.

Enhanced n-butanol production by Clostridium beijerinckii MCMB 581 in presence of selected surfactant.

Extractive butanol fermentation with non-ionic surfactant, a recently explored area, has shown promising results with several advantages but is relatively less investigated. This work reports the extractive fermentation with selected non-ionic surfactants (L62 and L62D) to enhance butanol production using a high-butanol producing strain (Clostridium beijerinckii MCMB 581). Biocompatibility studies with both the surfactants showed growth. Higher concentrations of surfactant (>5%) affected the cell count. 15.3 g L-1 of butanol and 21 g L-1 of total solvents were obtained with 3% (v/v) L62 which was respectively, 43% (w/w) and 55% (w/w), higher than control. It was found that surfactant addition at 9th h doubled the productivity (from 0.13 to 0.31 g L-1 h-1 and 0.17 to 0.39 g L-1 h-1, respectively for butanol and total solvent). Butanol productivity obtained was 2-3 times higher than similar studies on extractive fermentation with non-ionic surfactants. Interestingly, mixing did not improve butanol production.