Computational screening and molecular docking of compounds from Traditional Chinese Medicine (TCM) by targeting DNA topoisomerase I to design potential anticancer drugs

PLoS ONE, Год журнала: 2024, Номер 19(9), С. e0310364 - e0310364

Опубликована: Сен. 12, 2024

Each year thousands of people suffer across the globe due to higher cancer incidence and mortality rates. Additionally, treatment option for patients is also costly, often drugs from lower efficacy with more side effects. The DNA topoisomerase can function as an established target because Human Topoisomerase (Top1) regulates genetic transcription during post-mitotic phase plays a critical role in supercoiling replication repair. Therefore, drug therapy, blocking Top1 may be crucial inhibiting proliferation cells. Here, TCM (traditional Chinese medicine) compounds have been screened through virtual screening. medicine library’s screening process made it possible narrow down compound list 29 based on binding energy (-7.1 -9.3Kcal/mol), while following Lipniski filtering, MM/PB (GB) SA filtering was used screen remaining 22 top four were chosen free energy. compounds; CID-65752 (T2972: Rutaecarpine), CID-5271805 (T4S2126: Ginkgetin), CID-9817839 (T2S2335: Dehydroevodiamine) CID-51106 (T3054: Daurisoline) had comparatively -8.2, -8.5, -8.3 -8.2 respectively molecular docking than other compounds. Among these compounds, no toxic profile two found ADMET filtering. Moreover, SASA (solvent accessible surface area), Rg (radius gyrations), RMSD (root mean square deviation), RMSF fluctuation) drug-protein complex reveals stability rigidity dynamics simulation study. However, studies need validated experimental approaches develop potent effective drugs.

Язык: Английский

Antioxidant and antidiabetic effects of Flemingia macrophylla leaf extract and fractions: In vitro, molecular docking, dynamic simulation, pharmacokinetics, and biological activity studies

BioResources, Год журнала: 2024, Номер 19(3), С. 4960 - 4983

Опубликована: Июнь 5, 2024

Flemingia macrophylla has traditionally been applied to relieve inflammation, diabetes, and circulatory complications. The leaf extract of F. its fractions were investigated for their in-vitro antioxidant anti-diabetic properties. phytochemical screening showed valuable phytochemicals, including glycosides, flavonoids, saponins, etc. GC‒MS analysis the phytochemicals in methanol detected 19 bioactive compounds. Among diverse fractions, ethyl acetate fraction (EFM) exhibited highest phenol flavonoid contents 557 mg GAE/g 326 QCE/g, respectively. total content EFM was found be 292.41±19.16 AAE/g, while antidiabetic study greatest level α -glucosidase (IC50: 11.27±1.25 µg/mL) -amylase 10.04±0.63 inhibitory effects. docking results that C6 had binding scores -9.0, -7.4, -7.6 kcal/mol against (6NGJ), α-glucosidase (5NN5), α-amylase (4GQR) proteins, dynamics simulation disclosed C6-receptor protein complexes remained stable at pocket under human body conditions retained stiff morphology 100 nanoseconds (ns). ADMET demonstrated noncarcinogenic well-absorbed properties, where PASS prediction data confirmed efficacy as an antioxidant, antiulcerative, thrombolytic, antidiabetic. Therefore, potential health benefits.

Язык: Английский

In-vitro antioxidant and antidiabetic effects of Rorippa indica (L.) extract and fractions with molecular docking, dynamics simulation, ADMET, and PASS studies

Journal of Molecular Structure, Год журнала: 2024, Номер 1316, С. 138868 - 138868

Опубликована: Июнь 4, 2024

Язык: Английский