Isolation of phenolic compound from Lawsonia inermis and its prediction as anti-diabetic agent using molecular docking and molecular dynamic simulation.

High blood sugar is a defining feature of chronic disease, diabetes mellitus (DM). There are numerous commercially available medications for the treatment of DM. However, managing the patient's glucose levels remain a challenge because of the gradual reduction in beta-cell function and some side effects from the long-term use of various medications. Previous research has shown that the phenolic compound of henna plant (Lawsonia inermis L.) has the potential as anti-diabetic agent since it is able to suppress the digesting of α-amylase enzyme. In these studies, the plant' phenolic compounds have been isolated and characterized using UV, IR, NMR and LC-MS methods. Furthermore, the compound interaction into the active site of the α-amylase enzyme has been analyzed using molecular docking and molecular dynamics, as well as into α-glucosidase enzyme for predicting of the affinities. The results showed that isolated compound has the molecular formula of C15H10O6 with eleven degrees of unsaturation (DBE; double bond equivalence). The DBE value corresponds to the structure of the luteolin compound having an aromatic ring (8), a carbonyl group on the side chain (1) and a ketone ring with (2). The interaction study of the isolated compound with α-amylase and α-glucosidase enzyme using molecular docking compared to the positive control (acarbose) gave binding energy of -8.03 and -8.95 kcal/mol, respectively. The molecular dynamics simulation using the MM-PBSA method, complex stability based on solvent accessible surface area (SASA), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) revealed that the compound has a high affinity for receptors. The characteristics of skin permeability, absorption, and distribution using ADME-Tox model were also well predicted. The results indicate that the phenolic compound isolated from L. inermis leaf was luteolin and it has the potential as an anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Anti-Alopecia Activity of Coumarin Derivatives Isolated from Merremia peltata Leaves and Computational Study of Their Binding to Androgen Receptors Using Molecular Docking and Molecular Dynamic Simulation.

Alopecia is a condition in which hair on the scalp or other areas of the body is lost or falls out excessively. Nutritional deficiency causes blood flow to the head to decrease causing the hormone testosterone to be changed by the enzyme 5-α-reductase to dihydrotestosterone, which inhibits the growth phase and accelerates the death phase. One of the methods developed to treat alopecia is through inhibition of the 5-α-reductase enzyme, which converts testosterone to its more potent metabolite, dihydrotestosterone (DHT). Ethnomedicinally, Merremia peltata leaf is used by the people of Sulawesi as a remedy for baldness. Therefore, in this research, an in vivo study was conducted on rabbits to determine the anti-alopecia activity of M. peltata leaf compounds. The structure of the compounds isolated from the M. peltata leaf ethyl acetate fraction was determined by analysis of NMR and LC-MS data. An in silico study was then carried out using minoxidil as a comparison ligand; scopolin (1) and scopoletin (2) isolated from M. peltata leaf were identified as anti-alopecia compounds by predicting docking, simulating molecular dynamics and predicting absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox). Compounds 1 and 2 had a better effect on hair growth compared to positive controls, and NMR and LC-MS analysis showed that they had comparable binding energies to receptors in the molecular docking interaction study: -4.51 and -4.65 kcal/mol, respectively, compared to -4.8 kcal/mol for minoxidil. Molecular dynamics simulation analysis with the parameters binding free energy calculated using the MM-PBSA method and complex stability based on SASA, PCA, RMSD, and RMSF showed that scopolin (1) has a good affinity for androgens receptors. The ADME-Tox prediction for scopolin (1) showed good results for the parameters of skin permeability, absorption and distribution. Therefore, scopolin (1) is a potential antagonist to androgen receptors and could be useful in the treatment of alopecia.

Active Antialopecia Chemical Identification of Merremia peltata Leaves and Computational Study toward Androgen Receptor Using Molecular Docking and Molecular Dynamic Simulation.

Alopecia is a health condition in which the hair loses its function in some or all of the body. Alopecia occurs due to various genetic, environmental, and nutritional factors. One of the methods developed to treat alopecia is through inhibition of the enzyme 5-α-reductase, which converts testosterone into its more potent metabolite, dihydrotestosterone (DHT). In ethnomedicine, the leaves of Merremia peltata are used by the people of Sulawesi as a remedy for baldness. Therefore, in this study, an in vivo study was conducted on rabbits to investigate the antialopecia activity of the ethanolic extract of M. peltata leaves. The purified M. peltata leaf extract was fractionated using vacuum liquid chromatography with several solvents to produce fractions F1-F5. Each fraction was then retested in vivo in rabbits, and its content was then analyzed by LC-MS. An in silico study was then carried out using minoxidil as a comparison ligand; 17 compounds derived from M. peltata leaves were identified as antialopecia compounds through prediction of molecular interactions and molecular dynamics simulation and prediction of absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox). The assay results showed that fractions F2 and F3 had a better effect on hair growth compared to the positive control, and the test compound obtained from the LC-MS analysis, bufotalinin, had a strong binding energy to the receptor in the molecular docking interaction study: -5.99 kcal/mol compared to -4.8 kcal/mol for minoxidil. Molecular dynamics simulation analysis with complex stability parameters based on solvent-accessible surface area (SASA), principal component analysis (PCA), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) showed that bufotalinin has good affinity for androgen receptors. ADME-Tox prediction for bufotalinin showed good results for the parameters of skin permeability, absorption, and distribution. Therefore, bufotalinin, a steroid compound, is a potential androgen receptor antagonist and could be useful in the treatment of alopecia.

In silico analysis of marine natural product from sponge (Clathria Sp.) for their activity as inhibitor of SARS-CoV-2 Main Protease.

The target for COVID-19 has been successfully crystallized along with its inhibitor, named SARS-CoV-2 main protease, making it easier for drug discovery and development. Sponge (Clathria Sp.) is a marine species that can be found in Indonesia and has a unique chemical structure that is still rarely explored in its properties. Therefore, this study aims to examined the potential of marine natural products from sponge (Clathria Sp.) as SARS-CoV-2 main protease inhibitor using in silico method. The ligand structures were obtained from the Knapsack database and the protein structure obtained from the RCSB site with the PDB code: 6LU7. The molecular docking method was validated by re-docked the native ligand and calculated the RMSD value. The compounds contained in Sponge were docked into the active site of the protein based on the validated methods. Afterward, the molecular dynamics were performed for 100 ns simulation, then analyzed its system complex stability. The RMSD 1.329 Å was obtained by re-docked of native ligand which indicates that the docking method was valid. Molecular docking of the ligands showed mirabilin_G has binding energy -7.38 kcal/mol, compared to the native ligand N3 inhibitor that is -7.30 kcal/mol, and the ligand showed good stability from molecular dynamics simulation indicated by RMSD, RMSF and MM-PBSA binding free energy similar to the inhibitor during 100 ns simulation. Its indicated the potential of the compounds contained in the sponge as inhibitor of SARS-CoV-2 main protease.Communicated by Ramaswamy H. Sarma.

Molecular docking studies and ADME-Tox prediction of phytocompounds from Merremia peltata as a potential anti-alopecia treatment.

Alopecia is a condition in which some or all of the hair from the scalp is lost. One recent preventative measure is the inhibition of the enzyme 5-α-reductase. Inhibition of the enzyme 5-α-reductase converts circulating testosterone to its more potent metabolite, dihydrotestosterone. Ethnobotically, Merremia peltata is used as a baldness medicine by utilising compounds contained within the leaves. This research aimed to test activity of 18 known compounds contained within M. peltata) as anti-alopecia. Activity was based on their interaction with the androgen receptor (PDB code 4K7a) using molecular docking and ADME-Tox prediction. The stages of research performed were: preparation of androgen protein structure databases; preparation and optimization of three-dimensional structures of compounds using ChemDraw 8.0; molecular docking to the androgen receptor protein using Autodock 1.5.6.; and ADME-Tox prediction using the pkCSM tool. The following test compounds had strong bond energies (ΔG): compound 16 (olean-12-en-3beta-ol, cinnamate)-7.71 kcal/mol, compound 17 (alpha-amyrine)-6.34 kcal/mol, and Finasteride-6.03 kcal/mol. Interestingly, the ΔG of compound 16 (olean-12-en-3beta-ol, cinnamate) is better than of minoxidil (-4.8 kcal/mol) and also to gold-standard treatment compound, finasteride. ADME-Tox prediction for compound 16 showed favorable results in several metrics such as skin permeability, absorption, and distribution. Compound 16 (olean-12-en-3beta-ol, cinnamate) is therefore a potential androgen receptor antagonist and may be beneficial in the treatment of alopecia.

5,6-Dihydro-α-pyrones from the leaves of Cryptocarya pulchinervia (Lauraceae).

Three new 5,6-dihydro-α-pyrones derivatives, named (S)-rugulactone (1) pulchrinervialactone A (2), and pulchrinervialactone B (4), along with one known pyrone, cryptobrachytone C (3), and three known amide derivatives (5-7) have been isolated from the leaves of Cryptocarya pulchrinervia. The structures of 1-7 were elucidated based on extensive spectroscopic data and comparison with literatures. The configurations of compounds 3 and 4 were established by single crystal X-ray diffraction analysis. This is also the first report in finding (S)-rugulactone (1) as a natural product. In addition, the preliminary cytotoxic activity of the isolated compounds was evaluated against P-388 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. All the pyrones, except compound 4, were active significantly inhibiting the growth of P-388 cells, while the amides derivatives (5-7) showed moderate to weak activities. Therefore, compounds 1-3 could be potentially examined further for anticancer agents.