S. Merzouki, S. Boukeria, F. Louafi, M. H. Alma, R. Erenler, I. Yildiz, M. boulkroune, C. Mouats
{"title":"Physico-chemical and Biological Investigations of Ocimum Basilicum L. Cultivated in Algeria","authors":"S. Merzouki, S. Boukeria, F. Louafi, M. H. Alma, R. Erenler, I. Yildiz, M. boulkroune, C. Mouats","doi":"10.2174/0122127968300108240527090556","DOIUrl":"https://doi.org/10.2174/0122127968300108240527090556","url":null,"abstract":"\u0000\u0000This study aims to explore biologically active substances from natural\u0000sources, such as the Ocimum basilicum L. plant, for potential medicines. The LC-MS/MS analysis\u0000reveals that the majority of compounds in the aerial portion of this plant have Hesperidin and Vanillic\u0000acid, which are used in treating blood vessel fragility and neurological diseases (disorders) like\u0000Alzheimer's and Parkinson's.\u0000\u0000\u0000\u0000The study conducted a qualitative phytochemical screening of the hydromethanolic plant\u0000extract, revealing different secondary metabolites. Quantitative studies were conducted to determine\u0000the quantities of polyphenols, flavonoids, tannins, and alkaloids in the extract.\u0000\u0000\u0000\u0000Our investigations also assessed the antioxidant activity of the hydromethanolic plant extract\u0000using DPPH-free radical scavenging and cyclic voltammetry, providing insights into its potential\u0000to combat oxidative stress.\u0000\u0000\u0000\u0000Finally, the anticoagulant activity of the hydromethanolic plant extract was examined\u0000through Quick and Cephaline Kaolin time coagulation exploration tests, providing insights into its\u0000impact on coagulation pathways.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"185 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141388530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rushikesh Patel, A. K. Raj, K. Lokhande, Mrudula Joshi, Kratika Khunteta, Jayanta K. Pal, Nilesh Kumar Sharma
{"title":"Predicted Role of Acetyl-CoA Synthetase and HAT p300 in Extracellular Lactate Mediated Lactylation in the Tumor: In vitro and In silico Models","authors":"Rushikesh Patel, A. K. Raj, K. Lokhande, Mrudula Joshi, Kratika Khunteta, Jayanta K. Pal, Nilesh Kumar Sharma","doi":"10.2174/0122127968256108231226074336","DOIUrl":"https://doi.org/10.2174/0122127968256108231226074336","url":null,"abstract":"As per the Warburg effect, cancer cells are known to convert pyruvate into lactate. The accumulation of lactate is associated with metabolic and epigenetic reprogramming, which has newly been suggested to involve lactylation. However, the role of secreted lactate in modulating the tumor microenvironment through lactylation remains unclear. Specifically, there are gaps in our understanding of the enzyme responsible for converting lactate to lactyl-CoA and the nature of the enzyme that performs lactylation by utilizing lactyl-CoA as a substrate. It is worth noting that there are limited papers focused on metabolite profiling that detect lactate and lactyl-CoA levels intracellularly and extracellularly in the context of cancer cells. Here, we have employed an in-house developed vertical tube gel electrophoresis (VTGE) and LC-HRMS assisted profiling of extracellular metabolites of breast cancer cells treated by anticancer compositions of cow urine DMSO fraction (CUDF) that was reported previously. Furthermore, we used molecular docking and molecular dynamics (MD) simulations to determine the potential enzyme that can convert lactate to lactyl-CoA. Next, the histone acetyltransferase p300 (HAT p300) enzyme (PDB ID: 6GYR) was evaluated as a potential enzyme that can bind to lactylCoA during the lactylation process. We collected evidence on the secretion of lactate in the extracellular conditioned medium of breast cancer cells treated by anticancer compositions. MD simulations data projected that acetyl-CoA synthetase could be a potential enzyme that may convert lactate into lactyl-CoA similar to a known substrate acetate. Furthermore, a specific and efficient binding (docking energy -9.6 kcal/mol) of lactyl-CoA with p300 HAT suggested that lactyl-CoA may serve as a substrate for lactylation similar to acetylation that uses acetyl-CoA as a substrate. In conclusion, our data provide a hint on the missing link for the lactylation process due to lactate in terms of a potential enzyme that can convert lactate into lactyl-CoA. This study helped us to project the HAT p300 enzyme that may use lactyl-CoA as a substrate in the lactylation process of the tumor microenvironment.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139143787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tubulin-gene Mutation in Drug Resistance in Helminth Parasite: Docking and Molecular Dynamics Simulation Study","authors":"A. Swargiary, Harmonjit Boro, Dulur Brahma","doi":"10.2174/0122127968276934231219052232","DOIUrl":"https://doi.org/10.2174/0122127968276934231219052232","url":null,"abstract":"Drug resistance is an important phenomenon in helminth parasites. Microtubules are among the key chemotherapeutic targets, mutations of which lead to drug resistance. The present study investigated the role of F167Y, E198A, and F200Y mutations in βtubulin protein and their effect on albendazole binding. Brugia malayi β-tubulin protein models were generated using the SwissModel platform by submitting amino acid sequences. Mutations were carried out at amino acid sequences by changing F167Y, E198A, and F200Y. All the model proteins (one wild and three mutated) were docked with the anthelmintic drug albendazole using AutoDock vina-1.1.5. Docking complexes were further investigated for their binding stability by a Molecular Dynamic Simulation study using Gromacs-2023.2. The binding free energies of protein-ligand complexes were analyzed using the MM/PBSA package. The docking study observed decreased ligand binding affinity in F167Y and E198A mutant proteins compared to wild proteins. MD simulation revealed the overall structural stability of the protein complexes during the simulation period. The simulation also observed more stable binding of albendazole in the active pocket of mutant proteins compared to wild-type proteins. Like ligand RMSD, wild-type protein also showed higher amino acid residual flexibility. The flexibility indicates the less compactness of wild β-tubulin protein complexes compared to mutant proteinligand complexes. Van der Waals and electrostatic interactions were found to be the major energy in protein-ligand complexes. However, due to higher solvation energy, wild-type protein showed more flexibility compared to others. The study, therefore, concludes that mutations at positions 167 and 198 of the βtubulin protein contribute to resistance to albendazole through weakened binding affinity. However, the binding of albendazole binding to the proteins leads to structures becoming more stable and compact.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"87 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139151718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Therapeutic Potential: Antiplatelet and Antioxidant\u0000Activities of Some Medicinal Plants in Morocco","authors":"Lafdil Fatima Zahra, Amirou Asmae, Bnouham Mohamed, Legssyer Abdelkhaleq, Ziyyat Abderrahim, M. Hassane","doi":"10.2174/0122127968271295231212043119","DOIUrl":"https://doi.org/10.2174/0122127968271295231212043119","url":null,"abstract":"\u0000\u0000Thrombotic events and oxidative stress are major complications of certain\u0000ischemic disorders. The fight against these complications requires very intense research to develop\u0000new therapeutic agents of natural origin.\u0000\u0000\u0000\u0000The general objective of this work is the scientific valorization of five medicinal plants:\u0000Rhus pentaphylla, Zizyphus lotus, Ammodaucus leucotrichus, Inula viscosa, and Cinnamomum\u0000zeylanicum by exploring their effects on rat platelet aggregation, antioxidant potential and determining\u0000their phytochemical composition.\u0000\u0000\u0000\u0000e aggregation test was monitored by stimulating isolated washed platelets suspension\u0000in the absence and presence of extracts. The antioxidant activity was conducted in vitro according\u0000to three methods: DPPH free radical scavenging activity, β-carotene bleaching test, and ferric\u0000reducing antioxidant power test. The quantitative determination of total polyphenols and flavonoids\u0000are determined respectively according to the Folin-Ciocalteu method and the colorimetric method\u0000with aluminum chloride.\u0000\u0000\u0000\u0000The results obtained show that the aqueous extract of the fruits of Rhus pentaphylla and\u0000the aerial part of Inula viscosa, as well as the stalk peel of Cinnamomum zeylanicum, significantly\u0000(p˂0.001) inhibit thrombin-platelet aggregation, while the other plant extracts have a slightly, but\u0000significant effect. These extracts exert a remarkable antioxidant activity with the three methods\u0000used. But, their IC50 values are still higher than those of the antioxidant references (ascorbic acid\u0000and butyl hydroxyanisole). Qualitative phytochemical analysis revealed the presence of secondary\u0000metabolites with varying contents. Additionally, the results of quantitative phytochemical analysis\u0000showed that the aqueous extracts of the leaves of Rhus pentaphylla and the aerial part of Inula viscosa\u0000contain the highest amount of polyphenols and flavonoids. These secondary metabolites are\u0000also present in the other extracts but in smaller quantities.\u0000\u0000\u0000\u0000These results could contribute to the validation of the medical use of these extracts that\u0000exert an antiplatelet effect to treat hemostatic and thrombotic disorders.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":" 536","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138960596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}