CHARACTERIZATION AND MOLECULAR DOCKING OF CINNAMIC ACID DERIVATIVES: POTENTIAL INHIBITORS OF CYCLOOXYGENASE ENZYMES

Objective: The pathology of every disease passes through the inflammation stage; hence, the design and optimization of potential lead compounds as anti-inflammatory agents is still a significant part of medicinal chemistry globally. Methods: In this study, we designed, synthesized, and characterized some cinnamic acid derivatives and performed molecular docking of the derivatives on the human cyclooxygenase-1 (COX-1) enzyme. Results: The elemental analysis showed the presence of different functional groups. Molecular docking was performed on the active sites of COX-1 (PDB ID: 6Y3C). The derivatives as well as the standard compound, were observed to interact mainly with the arginine residue of the target protein. The dioxomethylene substituted derivative showed the highest binding affinity, compared with other derivatives, including the standard drug (−6.8 kcal/mol). Conclusion: The binding affinity observed in the cinnamic derivatives, and biological activities correlations revealed that compounds with the dioxomethylene group would be good anti-inflammatory lead molecules, as they demonstrated high affinity to the target protein and biological activities. Thus, these compounds can serve as potential lead compounds for the design, and development of effective anti-inflammatory agents, targeted to inhibit the human COX-1 enzyme involved in biological inflammatory mechanisms

Antimicrobial Properties and Characterization of Secondary Metabolites Obtained from Curvularia lunata, an Endophyte of Azadirachta indica

Background: Endophyte phytochemicals have piqued interest in drug development programs due to their enormous potential for assisting in the discovery of novel biologically active compounds. Aim and objectives: The study was aimed to isolate, evaluate the antimicrobial properties and characterize the secondary metabolites of Curvularia lunata endophyte isolated from A. indica. Method: C. lunata isolated from A. indica leaves using standard extraction protocols were screened for their potential antimicrobial activities using agar diffusion well method. HPLC-DAD, GC-FID, GC-MS, and FTIR techniques were used to characterize secondary metabolites. Results: At 1 mg/mL, growth inhibition of bacteria by the extracts of C. lunata were observed with Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Candida albicans with zones of inhibition diameters of 6, 5, 4, and 4 mm respectively.  The vacuum liquid chromatography sub-fraction of the extract showed the best antimicrobial activity. HPLC-DAD analysis revealed the presence of 2-carboxymethyl-3-n-hexylmaleic acid anhydride and aspernigin A. GC-FID analysis showed remarkably high concentrations of flavonones and catechins. The results of GC-MS analysis also showed the presence of hexadecanoic acid, and 1,6-Anhydro-beta-D-glucopyranose. FTIR results established the presence of functional groups like carboxylic acids, which may be associated with some of the detected compounds. Conclusion: C. lunata (OM337582) extract of A. indica have potent antimicrobial activity which could be related to a high content of flavonoids and alkaloids. Keywords: Antimicrobial, Azadirachta indica, HPLC-DAD, Chromatography, Curvularia lunata

Quantitative phytochemical analysis of the fungus endophytic extracts isolated from Azadirachta indica using gas chromatography- flame ionization detector

Background information: The phytochemicals of endophytes have generated substantial interest in drug discovery programs because they offer the possibility of discovering new biologically active molecules. Objective: The objective of this study was to quantify and analyze the phytochemical profile of the fungus endophytic extracts isolated from Azadirachta indica leaves, which have been used ethnobotanically for treating malaria and bacterial infections. Methods: Endophytic fungi were isolated, solid-state fermentation of rice medium was performed, and secondary metabolites were extracted according to standard techniques. An analytical system that uses gas chromatography and flame ionization detection (GC-FID) was used to determine the phytochemical constituents contained in the endophytes. Results: The results of GC-FID analysis showed the presence of Ribalinidine, Naringenin, Sparteine, Phenol, Steroids, Kaempferol, Flavone, Oxalate, Catechin, Tannin, and Rutin at different concentrations. Conclusion: This study reveals the promising ability of the endophytic fungi of A. indica as a foundation of naturally occurring bioactive. The quantitative phytochemical assessment of the endophyte extracts from the leaves of A.indica showed that endophyte extracts from the plant are rich in both alkaloids and flavonoids (Phenolics). Keywords: GC-FID, Phytochemical, Endophytes, Secondary metabolites, Fermentation