Structure-based approach: molecular insight of pyranocumarins against α-glucosidase through computational studies.

α-glucosidase is an enzyme that catalyzes the release of α-glucose molecules through hydrolysis reactions. Regulation of this enzyme can increase sugar levels in type-2 diabetes mellitus (DM) patients. Pyranocoumarin derivatives have been identified as α-glucosidase inhibitors. Through an in silico approach, this work studied the inhibition of three pyranocoumarin compounds against the α-glucosidase at the molecular level. Molecular docking and molecular dynamics simulation were performed to understand the dynamics behavior of pyranocoumarin derivatives against α-glucosidase. The prediction of free binding energy (ΔG bind) using the Quantum Mechanics/Molecular Mechanics-Generalized Born (QM/MM-GBSA) approach for each system had the following results, PC1-α-Glu: -13.97 kcal mol-1, PC2-α-Glu: -3.69 kcal mol-1, and PC3-α-Glu: -13.68 kcal mol-1. The interaction energy of each system shows that the grid score, ΔG bind, and ΔG exp values had a similar correlation, that was PC1-α-Glu > PC3-α-Glu > PC2-α-Glu. Additionally, the decomposition energy analysis (ΔG residue bind) was carried out to find out the contribution of the key binding residue. The results showed that there were 15 key binding residues responsible for stabilizing pyranocumarin binding with criteria of ΔG residue bind < -1.00 kcal mol-1. The evaluation presented in this work could provide information on the molecular level about the inhibitory efficiency of pyranocoumarin derivatives against a-glucosidase enzyme based on computational studies.

Nano Uncaria gambir as Chemopreventive Agent Against Breast Cancer.

Background: Breast cancer is one of the main causes of death in women. Uncaria gambir is an Indonesian herbal plant that can be used as an anti-cancer. However, herbal medicines have low bioavailability, which affects their bioactivity. Nanoencapsulation can increase bioavailability and stability of bioactive compounds in herbal medicines. Purpose: This recent finding tried to unravel anti-cancer and chemopreventive of U. gambir nano-encapsulated by Na-alginate. Study Design: U. gambir bioactive compounds were isolated and characterized using UV-Vis spectrometer, FTIR, NMR and HR-MS. U. gambir extract was nanoencapsulated using Na-alginate. Anti-cancer effect was assessed by MTT assay towards T47D cell. Meanwhile, a chemopreventive analysis was carried out in breast cancer mice-induced benzo[α]pyrene. The healthy mice were divided into 8 groups comprising control and treatment. Results: Elucidation of U. gambir ethyl acetate extract confirmed high catechin content, 89.34% (w/w). Successful nanoencapsulation of U. gambir (G-NPs) was indicated. The particle size of G-NPs was 78.40 ± 12.25 nm. Loading efficiency (LE) and loading amount (LA) of G-NPs were 97.56 ± 0.04% and 32.52 ± 0.01%, respectively. G-NPs had an EC50 value of 10.39 ± 3.50 µg/mL, which was more toxic than the EC50 value of extract towards the T47D cell line. Administration of 200 mg/kg BW G-NPs to mice induced by benzo[α]pyrene exhibited SOD and GSH levels of 13.69 ng/mL and 455.6 ng/mL. In addition, the lowest TNF-α level was 27.96 ng/mL. A dose of 100 mg/kg BW G-NPs could best increase CAT levels by 7.18 ng/mL. There was no damage or histological abnormalities found in histological analysis of the breast tissue in the group given 200 mg/kg BW G-NPs.

3,4,3'-Tri-O-methylellagic acid as an anticancer agent: in vitro and in silico studies.

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3'-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment. The characterization of the isolated T-EA compound was carried out using various spectroscopic methods. The in vitro evaluation showcased the inhibition activity of T-EA towards the T47D and HeLa cell lines with EC50 values of 55.35 ± 6.28 µg mL-1 and 12.57 ± 2.22 µg mL-1, respectively. Meanwhile, the in silico evaluation aimed to understand the interaction of T-EA with enzymes responsible for cancer regulation at the molecular level by targeting the hindrance of cyclin-dependent kinase 9 (CDK9) and sirtuin 1 (SIRT1) enzymes. T-EA showed a binding free energy towards the SIRT1 protein of ΔG bind (MM-GBSA): -30.98 ± 0.25 kcal mol-1 and ΔG bind (MM-PBSA): -24.07 ± 0.30 kcal mol-1, while that of CDK9 was ΔG bind (MM-GBSA): -29.50 ± 0.22 kcal mol-1 and ΔG bind (MM-PBSA): -25.87 ± 0.40 kcal mol-1. The obtained results from this research could be considered as important information on 3,4,3'-tri-O-methylellagic acid as a drug to treat cervical and breast cancers.

Anticancer potential of ß-sitosterol and oleanolic acid as through inhibition of human estrogenic 17beta-hydroxysteroid dehydrogenase type-1 based on an in silico approach.

The human estrogenic enzyme 17beta-hydroxysteroid dehydrogenase type-1 (HSD17B1) provides biosynthesis regulation of active estrogen in stimulating the development of breast cancer through cell proliferation. The ß-sitosterol is classified as a steroid compound and is actually a type of triterpenoid compound that has a similar structure to a steroid. This similarity provides a great opportunity for the inhibitor candidate to bind to the HDS17B1 enzyme because of the template similarity on the active site. Several in silico approaches have been applied in this study to examine the potential of these two inhibitor candidates. Pharmacokinetic studies showed positive results by meeting several drug candidate criteria, such as drug-likeness, bioavailability, and ADMET properties. A combination of molecular docking and MD simulation showed good conformational interaction of the inhibitors and HSD17B1. Prediction of binding free energy (ΔG bind) using the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) approach shows ΔG bind (kcal mol-1) of C1-HSD17B1: -49.31 ± 0.23 and C2-HSD17B1: -33.54 ± 0.34. Meanwhile, decomposition energy analysis (ΔG residue bind) suggested several key residues that were also responsible for the interaction with inhibitors, such as C1-HSD17B1 (six residues: Leu96, Leu149, Pro187, Met193, Val225, and Phe226) and C2-HSD17B1 (four residues: Ile14, Gly94, Pro187, and Val188). Hopefully, the obtained results from this research could be considered for the mechanistic inhibition of the HSDS17B1 enzyme at molecular and atomistic levels.

Tropical Medicinal Plant Extracts from Indonesia as Antifungal Agents against Candida Albicans.

BACKGROUND: Candida albicans is responsible for a wide range of medical ailments, from harmless cutaneous to life-threatening bloodstream infections. Growing cases of antifungal-drug resistance strains of C. albicans become a rationale to explore and develop novel anti-candida agents. In this paper, we assessed the anti-candida activity of the methanolic extracts of various tropical medicinal plants from Myrtaceae, Poaceae, and Zingiberaceae, commonly used in Indonesia to treat fungal infections. METHODS: Candida albicans strain ATCC 10231 was used as a subject to assess the anti-Candida activities of plant methanolic extracts through disc diffusion assay. Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) were observed. RESULTS: All plant extracts in this study showed antifungal activities against C. albicans. Among them, Cymbopogon citratus, Curcuma xanthorrhiza, Curcuma aeruginosa, and Zingiber officinale var. rubrum showed the lowest MIC and MFC value of 3.8 mg/mL. CONCLUSIONS: The growth inhibition of C. albicans on disc diffusion assay was demonstrated by Z. officinale var. rubrum and C. longa, which were comparable to antifungal nystatin. Further investigation of the chemical constituents of the extracts and the cytotoxicity test is needed to further develop plant-derived anti-candida agents.

The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies.

An investigation has been carried out on natural products from dolabellane derivatives to understand their potential in inhibiting the SARS-CoV-2 main protease (3CLpro) using an in silico approach. Inhibition of the 3CLpro enzyme is a promising target in stopping the replication of the SARS-CoV-2 virus through inhibition of the subsite binding pocket. The redocking process aims to determine the 3CLpro active sites. The redocking requirement showed a good pose with an RMSD value of 1.39 Å. The combination of molecular docking and MD simulation shows the results of DD13 as a candidate which had a good binding affinity (kcal mol-1) to inhibit the 3CLpro enzyme activity. Prediction of binding free energy (kcal mol-1) of DD13 using the Molecular Mechanics-Poisson Boltzmann/Generalized Born Surface Area (MM-PB/GBSA) approach shows the results ΔG bind(MM-GBSA): -52.33 ± 0.34 and ΔG bind(MM-PBSA): -43.52 ± 0.42. The key residues responsible for the inhibition mechanism are Hie41, Ser46, Met49, Asn142, Cys145, Hie163, Met165, and Gln189. Additionally, pharmacokinetic prediction recommended that DD13 had promising criteria as a drug candidate. The results demonstrated in this study provide theoretical information to obtain a potential inhibitor against the SARS-CoV-2 main protease.

Potential of diterpene compounds as antivirals, a review.

Viruses cause widely transmitted diseases resulting in pandemic conditions. Currently, the world is being hit by the Covid-19 pandemic caused by the SAR-CoV-2 infection. Countries in the world are competing to develop antivirals to overcome this problem. Diterpene compounds derived from natural ingredients (plants, corals, algae, fungi, sponges) and synthesized products have potential as antivirals. This article summarizes the different types of diterpenes such as daphnane, tiglilane, kaurane, abietane, pimarane, labdane, dollabelane, jatrophane, dolastane, prenylated guaiane, tonantzitlolone, casbane, have antivirals activity such as targeting HIV, Coxsackie virus, herpes virus, hepatitis virus, influenza virus, Chikungunya virus, Zika virus, dengue virus, and SARS-CoV. Some compounds such as andrographolide and its derivatives show promising activity in inhibiting the influenza virus. Additionally, compounds such as pineolidic acid, forskolin, sugiol, and many other diterpene compounds showed anti-SAR-CoV activity. The diterpene compound class's high antivirals potential does not rule out the possibility that these compounds can also act as anti-SAR-CoV-2 drugs in the future.