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In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.

ABSTRACT: Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3D structures of the derivatives were docked into the colchicine binding site of tubulin using GOLD 5.0 program under flexible ligand and semi-flexible receptor condition. The spiroisoxazoline derivatives bind tubulin in a similar manner to colchicine by establishing at least a hydrogen bonding to Cys(241) as well as hydrophobic interactions with Leu(255), Ile(378) and Lys(254) and few other residues at the binding pocket. It can be concluded that the spiroisoxazoline core structure common to the studied derivatives is a suitable scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial positions required for tubulin binding activity.

SUBMITTER: Abolhasani H

PROVIDER: S-EPMC4277627 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.

Abolhasani Hoda H Zarghi Afshin A Hamzeh-Mivehroud Maryam M Alizadeh Ali Akbar AA Shahbazi Mojarrad Javid J Dastmalchi Siavoush S

Iranian journal of pharmaceutical research : IJPR 20150101 1

Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3D structures of the derivatives were docked into the colchicine binding site of tubulin using GOL ...[more]

PMID: 25561920

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Project description:Phytochemicals are directly involved in therapeutic treatment or precursors to synthesize useful drugs. The current study was aimed to evaluate the phytocompounds and their biopotentials using methanolic and n-hexane extracts of various parts of Oxalis pes-caprae. For the phytochemical analysis, standard procedures were used, whereas Aluminum Chloride reagent and Follin-ciocalteau reagent methods were used to determine total flavonoid and phenolic contents. Radical scavenging DPPH, phosphomolybdenum reduction, and reducing power assays were used to assess antioxidative potentials. Antibacterial potential was determined by applying disc diffusion method while cytotoxicity was determined employing brine shrimp assay. FT-IR (Fourier-transform infrared) analysis was utilized to gather spectral information, while molecular docking tools were employed to look at how O. pes-caprae plant-based ligands interact with the target protein COVID-19 3CLPro (PDB:6LU7). Phenols, flavonoids, alkaloids and saponins were tested positive in preliminary phytochemical studies. TPC and TFC in different extracts ranging from (38.55 ± 1.72) to (65.68 ± 0.88) mg/g GAE/g and (24.75 ± 1.80) to (14.83 ± 0.92) mg/g QUE/g were used respectively. IC50 value (24.75 ± 0.76 g/mL) by OXFH, total antioxidant capacity (55.89 ± 1.75) mg/g by OXLM, reducing potential (34.98 ± 1.089) mg/g by OXSM, maximum zone of inhibition against B. subtilis (24 ± 0.65 mm) by OXLM and maximum cytotoxicity 96% with LD50 19.66 (μg/mL) by OXSM were the best calculated values among all extracts. Using molecular docking, it was found that Caeruleanone A, 2',4'-Dihydroxy-2″-(1-hydroxy-1-methylethyl) dihydrofuro [2,3-h] flavanone and Vadimezan demonstrated best affinity with the investigated SARS CoV-2 Mpro protein. This work provide justification about this plant as a source of effective phytochemicals and their potential against microbes could lead to development of biosafe drugs for the welfare of human being. In future, different in vitro and in vivo biological studies can be performed to further investigate its biomedical potentials.

Dataset Information

In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.

Publications

In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.

Similar Datasets

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