Unveiling the Bioactive Potential of Bacterial Isolates from Extreme Environments of Pakistan by In Vitro and In Silico Approaches.

The soil hosts a wide array of bacterial species capable of producing diverse bioactive compounds. This research aimed to screen bacterial isolates for their bioactive potential from extreme environments in Pakistan. Out of the 69 isolates examined, only 7 exhibited antagonistic activity against Bacillus sp. and Escherichia coli test strains. Notably, the B. cereus DS-2 strain demonstrated the highest antibacterial potential (31 mm and 15 mm) against the Bacillus and E. coli test strains, respectively. Mode-of-action studies suggested that the crude extract might have induced morphological abnormalities in the Bacillus sp. (test strain), causing cell contraction, chain breakage, and deformation. Furthermore, the B. cereus DS-2 strain displayed significant antioxidant potential (64.8%) as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Thin-layer chromatography (TLC) of the DS-2 crude extract led to the separation of six components, with only spots 3 and 4 exhibiting the antibacterial potential (3 mm and 5 mm, respectively). Subsequently, gas chromatography-mass spectrometry (GC-MS) analysis of the bioactive fraction extracted from TLC revealed the presence of diisooctyl phthalate, dibutyl phthalate, hexadecanoic acid methyl ester, and octadecanoic acid methyl ester. Molecular docking analysis of diisooctyl phthalate and dibutyl phthalate revealed their binding affinity against E. coli and Bacillus sp. targets. ADMET analysis confirmed the solubility, toxicity, and drug-like properties of the ligands based on Lipinski's rule of five. Current findings suggest that these compounds hold promise as antibacterial agents in drug development. This study underscores the diverse microbial community present in extreme environments and highlights the versatile applications of natural products derived from these strains.

Phytochemical, anti-hyperlipidemic and in silico studies of extracts of Ficus carica seeds.

Hyperlipidemia has been considered a disease primarily causing death along with other prevailing diseases such as coronary heart diseases, atherosclerosis and stroke. The present study aims to evaluate the anti-hyperlipidemic potential of Ficus carica. Extracts of seeds of Ficus carica were investigated for bioactive compounds and screened using in-vitro and in-vivo anti-hyperlipidemic activities. Fig seeds showed potential in-vitro by inhibition of pancreatic lipase while in-vivo study revealed that methanol extract of fig seeds exhibited the anti-hyperlipidemic property by beneficially modifying lipid profile of albino mice comparable to standard drug. GC-MS analysis of methanol extract of seeds of Ficus carica exhibited a variety of bioactive compounds. After further evaluation of ligands for their activity by using molecular docking and MM-GBSA study, it is concluded that 1,2,3-benzentriol has the highest binding affinity for pancreatic lipase enzyme. Hence, it is concluded that seeds of Ficus carica are medicinally important and have promising anti-hyperlipidemic potential.

The Potential of Stilbene Compounds to Inhibit Mpro Protease as a Natural Treatment Strategy for Coronavirus Disease-2019.

COVID-19 disease has had a global impact on human health with increased levels of morbidity and mortality. There is an unmet need to design and produce effective antivirals to treat COVID-19. This study aimed to explore the potential ability of natural stilbenes to inhibit the Mpro protease, an acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enzyme involved in viral replication. The binding affinities of stilbene compounds against Mpro were scrutinized using molecular docking, prime molecular mechanics-generalized Born surface area (MM-GBSA) energy calculations, and molecular dynamic simulations. Seven stilbene molecules were docked with Mpro and compared with GC376 and N3, antivirals with demonstrated efficacy against Mpro. Ligand binding efficiencies and polar and non-polar interactions between stilbene compounds and Mpro were analyzed. The binding affinities of astringin, isorhapontin, and piceatannol were -9.319, -8.166, and -6.291 kcal/mol, respectively, and higher than either GC376 or N3 at -6.976 and -6.345 kcal/mol, respectively. Prime MM-GBSA revealed that these stilbene compounds exhibited useful ligand efficacy and binding affinity to Mpro. Molecular dynamic simulation studies of astringin, isorhapontin, and piceatannol showed their stability at 300 K throughout the simulation time. Collectively, these results suggest that stilbenes such as astringin, isorhapontin, and piceatannol could provide useful natural inhibitors of Mpro and thereby act as novel treatments to limit SARS-CoV-2 replication.

Terpyridine-metal complexes: effects of different substituents on their physico-chemical properties and density functional theory studies.

A series of different substituted terpyridine (tpy)-based ligands have been synthesized by Kröhnke method. Their binding behaviour was evaluated by complexing them with Co(II), Fe(II) and Zn(II) ions, which resulted in interesting coordination compounds with formulae, [Zn(tpy)2]PF6, [Co(tpy)2](PF6)2, [Fe(tpy)2](PF6)2 and interesting spectroscopic properties. Their absorption and emission behaviours in dilute solutions were investigated in order to explain structure-property associations and demonstrate the impact of different aryl substituents on the terpyridine scaffold as well as the role of the metal on the complexes. Photo-luminescence analysis of the complexes in acetonitrile solution revealed a transition from hypsochromic to bathochromic shift. All the compounds displayed remarkable photo-luminescent properties and various maximum emission peaks owing to the different nature of the functional groups. Furthermore, the anti-microbial potential of ligands and complexes was evaluated with docking analyses carried out to investigate the binding affinity of terpyridine-based ligands along with corresponding proteins (shikimate dehydrogenase and penicillin-binding protein) binding sites. To obtain further insight into molecular orbital distributions and spectroscopic properties, density functional theory calculations were performed for representative complexes. The photophysical activity and interactions between chromophore structure and properties were both investigated experimentally as well as theoretically.