Carbohydrate derivatives play a pivotal role in pharmaceutical chemistry as valuable scaffolds for the development of bioactive compounds. A unique series of p-tolyl-β-D-galactopyranoside derivatives was prepared via direct acylation of methyl β-D-galactopyranoside (1, MβDG), followed by the conversion into tri-substituted derivatives using various acyl halides in excellent yields. The structures and conformations of the synthesized derivatives were characterized by FTIR, 1H NMR, and 13C NMR spectroscopy. Derivatives 7 and 9 showed moderate antibacterial activity, with MICs of 0.25–16.0 μg/mL and MBCs of 8.0–128.0 μg/mL against Salmonella typhi and Klebsiella pneumoniae, respectively. Among these derivatives, compound 7 strongly inhibited the mycelial growth of both Aspergillus niger (82.50%) and Candida albicans (75.92%). Compound 6 showed antibiofilm activity against Escherichia coli, and compounds 8 (IC50 = 3735.85 μg/mL) and 9 (IC50 = 7485.27 μg/mL) had anticancer activity against Ehrlich ascites carcinoma (EAC) cells. Compounds 4 (73.43%) and 7 (71.54%) presented the highest anti-inflammatory activity. The antioxidant activity was displayed by compounds 8 (36.0%) and 2 (33.0%). Molecular docking is executed to describe the binding affinities and interactions between the MβDG derivatives and the enzyme (MurF) and ALS3 protein. The binding affinities of derivatives 8 and 9 toward MurF were −9.2 and −9.0 kcal/mol, respectively, while those of derivatives 6 and 8 toward ALS3 were −9.3 and −9.1 kcal/mol, respectively. The improved derivatives strongly interact with different protein residues. The docked complexes underwent MD simulations to assess their stability. Structure–activity relationship (SAR) analysis revealed that the incorporation of {3-Cl.C6H4·CO-} > {2-Cl.C6H4. CO-} > {3,5-(NO2)2C6H3CO-} substituents on the galactose moiety or galactopyranoside skeleton moiety progressively enhanced the antimicrobial activity. The extrapolation of ADMET and its medicinal attributes showed substantial outcomes because of favorable kinetic properties. These MβDG derivatives may serve as moderate inhibitors against various microorganisms and as prospective drug candidates for future development.
This study was designed to identify phytocompounds from the methanolic extract of Saraca asoca (Roxb.) Willd bark using GC–MS analysis against Heavy Menstrual Bleeding (Menorrhagia) PPAR-γ target protein. Pharmacokinetic properties were also tested for the identified phytocompounds to evaluate the ADMET properties. Molecular docking studies were done using Schrodinger suite (Maestro 11.2 Version), and ADMET properties of phytocompounds were evaluated using Qikprop. From the results, 15 best compounds were identified from GC–MS analysis against Heavy Bleeding Disorder (Menorrhagia) PPAR-γ target protein. Of these, the top 10 phytocompounds showed very good binding affinity with the PPAR-γ target protein. They are 11,14,17-Eicosatrienoic acid, methyl ester −6.896 kcal/mol, Caryophyllene oxide −5.589/kcal/mol, Hydroxy caryophyllene −5.507 kcal/mol Phenol, 2-methoxy- 3-(2-propenyl −5.308 kcal/mol and Copaene −5.223 kcal/mol. Further, docking study was performed for the synthetic drug Tranexamic acid to compare the efficiency of phytocompounds. The binding affinity of 11,14,17-Eicosatrienoic acid, methyl ester −6.896 kcal/mol is higher than the synthetic drug Tranexamic acid (−2.61 kcal/mol), and the binding affinity of other compounds is also very near to that of the drug. Hence, in the present study, we first and foremost conclude that the phytocompounds from the methanolic bark extract of S . asoca have the potential ability to treat Heavy Bleeding Disorder (Menorrhagia) through PPAR-γ target protein. According to this study, it's interesting to note that the 11,14,17-Eicosatrienoic acid, methyl ester ligand as determined by molecular dynamics simulation in terms of total binding energy has the ability to inhibit the PPAR-γ target protein. This study provides new insights into the potential of S. asoca for treating menstrual disorders, particularly PPAR-γ target protein, supporting further investigation and therapeutic development in drug discovery.
Models capable of interpreting the acid-base properties of blood are either very complex and counterintuitive or simplistic and insufficient to describe the different types of experiments that can be carried out, or to fully justify the commonly used, empirically-based clinical concepts. Physico-chemical models, however, may be drastically simplified while retaining great predictive capabilities. In this paper I demonstrate that the mathematical treatment for a complex mixture of buffers developed by Nguyen and co-workers [Nguyen, M. K. , Kao, L. , & Kurtz, I. (2009). Am. J. Physiol. - Renal Physiol., 296, F1521–F1529] combined with the intuition by Stewart that the acid-base chemistry of blood may be described by just two buffers [Stewart, P. (1978) Resp. Physiol., 33: 9–26], approaches the goal of a rigorous and simple interpretation of the acid-base chemistry of blood in vitro , and may also be able to predict some in vivo properties of blood. The mathematical model presented in this work provides a quantitative description of the most important experiments that can carried out in vitro (e.g. the titration of blood with PCO 2 , strong acids and strong bases both at constant PCO 2 or at constant total CO 2 content), and can interpret, with some approximation, also the gas exchanges in vivo .
This study was designed to identify phytocompounds from the methanolic extract of Saraca asoca (Roxb.) Willd bark using GC–MS analysis against Heavy Menstrual Bleeding (Menorrhagia) PPAR-γ target protein. Pharmacokinetic properties were also tested for the identified phytocompounds to evaluate the ADMET properties. Molecular docking studies were done using Schrodinger suite (Maestro 11.2 Version), and ADMET properties of phytocompounds were evaluated using Qikprop. From the results, 15 best compounds were identified from GC–MS analysis against Heavy Bleeding Disorder (Menorrhagia) PPAR-γ target protein. Of these, the top 10 phytocompounds showed very good binding affinity with the PPAR-γ target protein. They are 11,14,17-Eicosatrienoic acid, methyl ester −6.896 kcal/mol, Caryophyllene oxide −5.589/kcal/mol, Hydroxy caryophyllene −5.507 kcal/mol Phenol, 2-methoxy- 3-(2-propenyl −5.308 kcal/mol and Copaene −5.223 kcal/mol. Further, docking study was performed for the synthetic drug Tranexamic acid to compare the efficiency of phytocompounds. The binding affinity of 11,14,17-Eicosatrienoic acid, methyl ester −6.896 kcal/mol is higher than the synthetic drug Tranexamic acid (−2.61 kcal/mol), and the binding affinity of other compounds is also very near to that of the drug. Hence, in the present study, we first and foremost conclude that the phytocompounds from the methanolic bark extract of S. asoca have the potential ability to treat Heavy Bleeding Disorder (Menorrhagia) through PPAR-γ target protein. According to this study, it's interesting to note that the 11,14,17-Eicosatrienoic acid, methyl ester ligand as determined by molecular dynamics simulation in terms of total binding energy has the ability to inhibit the PPAR-γ target protein. This study provides new insights into the potential of S. asoca for treating menstrual disorders, particularly PPAR-γ target protein, supporting further investigation and therapeutic development in drug discovery.
Natural products continue to provide valuable scaffolds for antimalarial drug discovery because of their structural diversity and biological relevance. Due to the rapid sequestration of parasite-infected red blood cells and catastrophic blood–brain barrier (BBB) breakdown, cerebral malaria, the most deadly neurovascular complication caused by Plasmodium falciparum , has alarmingly high death rates worldwide. This study employed a pharmacophore-based in silico strategy to design HMI-CFPB, a scaffold-hopped analogue of acteoside derived from Spathodea campanulata , with enhanced BBB penetration and multistage antiplasmodial potential. Computer-aided scaffold hopping was deployed to replace the bulky glycosidic core with a pharmacologically optimized scaffold. The generated analog, HMI-CFPB, was rigorously evaluated using in silico ADMET filters, molecular docking simulations against vital multi-stage targets which include P. falciparum cGMP-dependent protein kinase (PfPKG), P. falciparum phosphatidylinositol 4-kinase (PfPI4K) for asexual blood stages and AKT Serine/Threonine Kinase 1 (AKT1) for transmission stages and comprehensive 100-ns MDs to ascertain binding stability. In silico optimization delivered significant pharmacokinetic and therapeutic enhancements. Structural scaffold replacement successfully reduced the polar surface area topological polar surface area (TPSA ≤140 Å 2 ) achieving an optimal lipophilicity (LogP ≤5) demonstrating robust passive trans-cellular diffusion across BBB endothelial models. HMI-CFPB displayed exceptional binding affinities against the respective targets (with a binding score of −8.7 kcal/mol for PfPKG, −8.3 kcal/mol for PfPI4K and −10.5 kcal/mol for AKT1) significantly outperforming native inhibitors. MD simulations corroborated these findings, showing minimal root-mean-square deviation (RMSD) fluctuations and stable hydrogen-bonding networks over 100 ns. The scaffold-hopping approach successfully generated a chemically optimized analogue with improved pharmacodynamic and pharmacokinetic characteristics suitable for central nervous system accessibility and multistage antimalarial intervention. These findings highlight HMI-CFPB as a promising lead candidate for further in vitro and in vivo validation in the development of next-generation antimalarial therapeutics targeting resistant P. falciparum infections.
