In silico docking and Molecular Dynamic (MD) simulations studies of selected phytochemicals against Human Glycolate Oxidase (hGOX) and Oxalate oxidase (OxO).

Globally, Urolithiasis is the most prevalent urological problem which affects the populations across the ages and races. In recent years, several phytochemicals are being investigated to improve the efficacy and safety of anti-urolithiasis formulations. To develop drugs based on traditional medicines, it is essential to understand the molecular mechanism of action of these drugs. We present the results of in silico docking and molecular dynamic (MD) simulation studies on selected phytochemical including catechin, epicatechin, gallic acid, gallocatechin, epigallocatechin, epigallocatechin 3-o-gallate, 4-methoxy-nor-securine, nor-securinine, and fisetin with human glycolate oxidase (hGOX) and oxalate oxidase (OxO). Gallic acid, gallocatechin and fisetin showed better docking scores than the rest. In MD simulation analysis, stable interactions of the gallic acid with hGOX and OxO; gallocatechin and fisetin with hGOX were observed. It was found that, gallic acid stably interacts withTYR26, LYS 236, ARG 315, and ASP 291 residues of hGOX. On other hand, gallic acid stably interacs with GLU 58 residue of OxO. Gallocatechin, forms stable interactions with TYR 26, ASP 170, ARG 167 and THR 161 of HGOX. In MD simulations, fisetin stably interacted with TYR 26, TRP110 and ARG 263 as we predicted in molecular docking. None of the interactions was formed during the MD simulation of OxO with gallocatechin and fisetin. Together, these results suggest that gallic acid, gallocatechin and fisetin are the potential candidates for the development of phytochemicals for the management of urolithiasis in humans.

Screening of Phyllanthus niruri Plant Active Constituents for Anticancer and Antifungal Activity by Insilico Methods.

A large genus of shrubs, trees, and rare plants belonging to the Euphorbiaceae family, Phyllanthus contains 600-700 species. The Phyllanthus niruri (L.) species is a tiny, erect annual herb that can reach heights of 30-40 cm. Its 7-12 cm long, sessile, alternating leaves are native to the Amazon rainforest, but they can also be found in other tropical regions such as South East Asia, Southern India, America, China, and the islands of the Indian Ocean. Phyllanthus contains many classes of alkaloids, steroids, flavonoids, lignin, polyphenols, and lipids. Numerous activities of the plant have been studied, including antidepressant (Wasnik et al., Int J Pharm Sci Rev Res, 6:26-29, 2014), anticancer (Sayuti et al. Studies, 10:17, 2020), anti-inflammatory, antinociceptive (Porto et al., Revista Brasileira de Farmacognosia, 23:138-144, 2013), analgesic (Bhat et al., Pharm Res, 7:378, 2015), antiarthritic (Mali et al., Biomed Aging Pathol, 1:185-190, 2011), immunomodulatory, antibacterial, antifungal (Shilpa et al., Environm Dis, 3:63, 2018), antidiabetic (Kumar et al., Biomed Pharm J, 12:57-63, 2019), antiulcer (Mostofa et al., BMC Complement Altern Med, 17:1-10, 2017), antiviral (Wahyuni et al., Malays Appl Biol, 48:105-111, 2019), antiplasmodial (Ifeoma et al., Asian Pacific J Trop Med, 6:169-175, 2013), anticonvulsant (Amaechina and Omogbai, Nig J Nat Prod Med, 17:61-65, 2013), and hepato human cytochrome P450 CYP17A1 in association with abiraterone [PDB ID: 3RUK] plant extracts. New selective androgen receptor modulators were synthesized, and they were biologically evaluated (SARMs) (Micah et al., J Veter Med Anim Health 5(1):8-15, 2013, Rusmana et al., Indonesian Biomed J 9(2):84-90, 2017, Al Zarzour et al., Nutrients 10(8):1057, 2018, Khanna J Ethnopharmacol 82(1):19-22, 2002). In the present study [PDB ID: 3RUK,5T8E] with anticancer and [PDB ID: 6F0E,1EA1] with antifungal activities were used for docking study. In this study fluconazole's antifungal activity and dacarbazine's anticancer activity were used as benchmarks for molecular docking with Schrodinger 13.0 to compare the activity of Phyllanthus niruri's active constituents.

Screening of Phyllanthus niruri Root Phytoconstituents for Antibacterial, Antifungal, Anticancer, and Antiviral Activities by Molecular Docking Studies.

The systematic exploitation of the structural variety of natural products is made possible by docking studies, which have been shown to be a crucial technique. This study's goal was to evaluate various activities for the chemicals in the root portion of Phyllanthus niruri. This plant's constituents are active in a variety of ways. In order to develop drugs, molecules with such a framework have been utilized as the lead. Schrodinger Maestro (v13.0) software was used to conduct a molecular docking analysis of root components with certain proteins linked to the illnesses. In comparison to commercially available conventional medications, molecular docking data also demonstrated greater scores. For additional docking investigations with distinct proteins, the root chemicals are assessed, that is, crystal structure of serine protease hepsin in complex with inhibitor [PDB ID:5 CE1] for antiviral activity, human topoisomerase II beta in complex with DNA and etoposide [PDB ID:3QX3], and crystal structure of E. coli GyraseB 24 kDa in complex with 4-(4-bromo-1H-pyrazol-1-yl)-6-[(ethylcarbamoyl)amino]-N-(pyridin-3-yl) pyridine-3-carboxamide [PDB ID: 6F86] for antibacterial activity, Cytochrome P450 14 alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with fluconazole [PDB ID:1EA1], and structure of yeast Sec14p with a picolinamide compound [PDB ID:6F0E] for antifungal activity and synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl) benzonitrile derivatives [PDB ID: 5T8E] and Human Cytochrome P450 CYP17A1 in complex with Abiraterone [PD B ID:3RUK] for anticancer activity have been selected. Ritonavir's antiviral activity, ampicillin's ability to treat bacterial infections, fluconazole's ability to treat fungi, and dacarbazine's ability to treat cancer were utilized as benchmarks to assess the in silico outcomes and grading of virtual screening or molecular docking.