The methyl α-D-glucopyranoside and its derivatives have been estimated as the antimicrobial agents against numerous human pathogens, which is constantly amplifying the attention of medicinal chemists to design new bioactive molecules and their structure-activity relationship (SAR) while the computational tools are the most lucid and trustable avenue to perform their theoretical profile building up. Firstly, the predictionof activity spectra for substances (PASS) value has illustrated initially information about the antifungal, antibacterial, antiviral, and anticancer potential. It was observed that the PASS predicted pathogens supported their score higher in fungal species than bacteria. However, the “Lipinski five rule” has been monitored for drug-likeness properties. After confirming their biological significance, molecular docking has been completed against both the bacteria and fungi and these docked complexes have been optimized for molecular dynamics through the water system. A molecular docking study against nine bacterial and fungal pathogens revealed promising binding affinity and non-bonding interaction mostly for derivatives (5-8). The chemical descriptors have been obtained using the density functional theory (DFT) and predict their chemical stability and softness in the biological system. The molecular dynamics study was found to be the best stability of all docked complexes. At last, the ADMET properties have been calculated and provide the safe use and non-carcinogenic fact with low toxicity for both aquatic and non-aquatic species. Finally, it is concluded that these selected derivatives (5-8) are highly antifungal potential molecules than antibacterial potential which has been varied with respect to their structural side chain in the D-glucopyranoside sequence.

The thiosemicarbazones and their derivatives have been recognized as antimicrobial agents against human pathogenic bacteria and fungi. Regarding these prospective, this study was designed to address the new antimicrobial agents from thiosemicarbazones and their derivatives. These derivatives were synthesized by multi-step synthesis methods, such as alkylation, acidification, esterification, and formed the 4-(4′-alkoxybenzoyloxy) thiosemicarbazones and its derivatives (THS1, THS2, THS3, THS4, and THS5). Afterward the synthesis, compounds were characterized by ¹H NMR, FTIR spectra, and melting point. Later, the computational tools were applied to evaluate the drug likeness properties, bioavailability score, Lipinski rule, absorption, distribution, metabolism, excretion, and toxicity (ADMET). Secondly, the quantum calculations, for instance HOMO, LUMO and chemical descriptors, were calculated by the density functional theory (DFT). Finally, the molecular docking was performed against seven human pathogenic bacteria, black fungus (Rhizomucor mieh, Mucor lusitanicus, Mycolicibacterium smegmatis) and white fungus strains (Candida Auris, Aspergillus luchuensis, Candida albicans). To check and validate of molecular docking procedure and stability of docked complex for ligand and protein, the molecular dynamic was performed of docked complex. From the docking score with calculating the binding affinity, these derivatives could show a higher affinity than standard drug against all pathogens. From the computational details, it could be decided to do in-vitro test as antimicrobial activity against Staphylococcus aurious, Staphylococcus homonis, Salmonella typhi, and Shigella flexneria. The obtained result of antibacterial activity compared to standard drugs, and it was found that the synthesized compounds were almost same value of standard drug. Finally, it could be said from the in-vitro and in-silico study that the thiosemicarbazones derivatives are good antimicrobial agents.

Structural modifications of ethyl-3-((5-bromopyridin-2-yl)imino)butanoate ester enhances its biological activities. In the present work, the synthesis of a Schiff base by reacting 2-amino-5-bromo pyridine and ethyl acetoacetate was reported. Electronic properties were investigated by the computational method of density functional theory (DFT). The pass prediction score supported anti-viral efficacy which satisfied the Lipiniski rule and overall HOMO-LUMO. The most important part of this investigation was docking study which revealed that the ligands L07 has nearly efficacy to standard drugs and maximum docking score was found against Alpha variant (7EKF) at −6.7 kcal/mol, Beta variant (7ekg) at −6.2 kcal/mol, Gamma variant (7EKC) at −6.5 kcal/mol, Beta variant (7ekg) at −6.2 kcal/mol, SARS-CoV-2 Gamma variant (7EKC) at −6.2 kcal/mol, Delta variant (7V8B) at −6.1 kcal/mol and Omicron variant (7T9J) at −6.3 kcal/mol. Finally, molecular dynamics study was performed to determine the stability and it was reported that the molecules L07 has better stability to be an oral drug against the different variant of SARS-CoV-2 viral pathogen.

B: Black fungus is the foremost life-threatening disease during the SARS-CoV-2 affected patients and spreading quickly in the region of the subcontinent of India although there was no prescribed proper medication. As the D-glucofuranose and its derivatives are reported to show strong antifungal activity, this study has been designed with them for their computational investigation. Firstly, the overall prediction of activity spectra for substances (PASS) value illustrates a good probability to be active (Pa) and probability to be inactive (Pi) value. Next, pharmacokinetics parameters including drug-likeness and Lipinski's rules, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and overall quantum calculation of computational approaches by Density Functional Theory (DFT) have gradually been performed to analyze quantum calculations. After the analysis of docking score, it is found at -9.4 kcal/mol, -7.5 kcal/mol, -7.8 kcal/mol, -8.5 kcal/mol against the strain of black fungus protein strains Mycolicibacterium smegmatis, Mucor lusitanicus, Rhizomucor mieh, and white fungus protein Candida Auris, Aspergillus luchuensis and Candida albicans. Next, the molecular dynamics of docked complexes have been performed to check their stability in biological systems with water ranging 100 ns calculating the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) where the minimum RMSD and RMSF value indicated the higher stable configuration of docked complexes. These compounds have perfectly matched all the pharmacokinetics criteria to be a good drug candidate against both black and white fungus, and they are non-carcinogenic, low solubility, low toxic for both aquatic and non-aquatic. In addition, the quantum calculation using DFT conveys the strongest support and information about their chemical stability and biological significance. Finally, it could be concluded that the carboxylic group and methyl group in the benzene ring causes higher binding affinity against black and white fungus protein strain through the formation of hydrogen and hydrophobic bonds.

Lung cancer (LC) is one of the major and risky health defects even the serious cause for death in concurrent era. But no potential drugs even chemotherapeutic agents have been discovered with approval of health safety although some non-toxic biological macromolecules, such as polysaccharides and polysaccharide–protein complexes, have obtained as anti-lung cancer properties. This study conveys the anti-lung cancer properties of 45 polysaccharide derivatives collected from PubChem database. Primarily, the PASS prediction was performed to depict their anti-cancer activity, and 37 compounds showed the desired results. Next, the chemical descriptors, such as HOMO, LUMO, softness, and hardness etc, were calculated through the density functional theory (DFT) for quantum properties. Secondly, the auto molecular docking was executed to delineate the protein-ligand interactions, binding ability and inhibition of active sites of proteins. Additionally, the compounds showed docking score more than −6.40 kcal/mol, and the highest binding affinity was at −10.00 kcal/mol even 15 compounds have higher binding score (-8.6 to −10.0) than approved drugs, Gemcitabine. Succeeding, the most common protein residue, VAL 647, was blocked by ligands for the main protein (1X2J). In addition, five protein’s active sites were determined to make the relative study of protein-ligand interactions. As a result, the target docking against five proteins was performed, and it was found that the targeted docking score as the binding affinity is lower than auto docking. Finally, a comparative study between auto docking and targeted docking was performed for the most common five lung cancer proteins founded in three organisms. Graphical Abstract Communicated by Ramaswamy H. Sarma