Molecular docking and dynamic simulations of benzimidazoles with beta-tubulins

Rao, Chennu Maruthi Malya Prasada; Naidu, Narapusetty; Priya, J Padma; Rao, K Poorna Chandra; Ranjith, Kapu; Shobha, S. V.; Chowdary, B. Sudheer; Siddiraju, Sridhar; Yadam, Sabitha

doi:10.6026/97320630017404

Cited by 16 publications

(2 citation statements)

References 14 publications

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“…Several solved p38α MAPK structures can be found in the Protein data bank (PDB) database [14][15]. The PDB ID: 1A9U protein structure was solved using x-ray diffraction at 2.5 resolution and is bound to the inhibitor SB203580.…”

Section: Resultsmentioning

confidence: 99%

Insights from the molecular docking and simulation analysis of P38 MAPK phytochemical inhibitor complexes

Rao¹

2023

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It is of interest to develop p38α MAPK inhibitors. Docking, ADMET properties calculation, molecular dynamics, and MM-PBSA approaches were used to investigate the therapeutic potentials of p38α MAPK in complex with SB203580 (1A9U). The photo-molecules metergoline, withaphysacarpin, philadelphicalactone, canthin-6-one 9-glucoside, and SB-21600011 demonstrated high binding affinity compared to the reference drug. Furthermore, ADME profiles validated the drug-like properties of the prioritized phyto-compounds. Besides that, MD simulations were performed along with reference inhibitors for withaphysacarpin and metergoline to assess stability. Binding free energy calculations (MM-PBSA) revealed that metergoline and withaphysacarpin had estimated values (G) of 97.151 ± 21.023 kJ/mol and -82.084 ± 15.766 kJ/mol, respectively. In this study, metergoline and withaphysacarpin were found to have high affinity against p38α MAPK when compared to the reference compound SB 203580.

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Section: Resultsmentioning

confidence: 99%

Insights from the molecular docking and simulation analysis of P38 MAPK phytochemical inhibitor complexes

Rao¹

2023

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“…As such, when the conformation of a ligand after an MD simulation deviates by more than a specific RMSD value from the initial docking prediction, the docking pose can be regarded as unstable even though it has a high docking score [ 27 , 30 ]. Since MD has been described as useful for assessing the stability of several tubulin colchicine site binders, including combretastatin analogs [ 31 ] and benzimidazoles [ 32 ], as well as for investigating DAMA-colchicine binding to different tubulin isotypes [ 33 ], using such a strategy to validate molecular docking poses in the case of pyrrole-fused derivatives could be useful in the future development of more potent tubulin inhibitors containing this scaffold.…”

Section: Introductionmentioning

confidence: 99%

Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach

et al. 2023

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Five new series of pyrrolo-fused heterocycles were designed through a scaffold hybridization strategy as analogs of the well-known microtubule inhibitor phenstatin. Compounds were synthesized using the 1,3-dipolar cycloaddition of cycloimmonium N-ylides to ethyl propiolate as a key step. Selected compounds were then evaluated for anticancer activity and ability to inhibit tubulin polymerization in vitro. Notably, pyrrolo[1,2-a]quinoline 10a was active on most tested cell lines, performing better than control phenstatin in several cases, most notably on renal cancer cell line A498 (GI50 27 nM), while inhibiting tubulin polymerization in vitro. In addition, this compound was predicted to have a promising ADMET profile. The molecular details of the interaction between compound 10a and tubulin were investigated through in silico docking experiments, followed by molecular dynamics simulations and configurational entropy calculations. Of note, we found that some of the initially predicted interactions from docking experiments were not stable during molecular dynamics simulations, but that configurational entropy loss was similar in all three cases. Our results suggest that for compound 10a, docking experiments alone are not sufficient for the adequate description of interaction details in terms of target binding, which makes subsequent scaffold optimization more difficult and ultimately hinders drug design. Taken together, these results could help shape novel potent antiproliferative compounds with pyrrolo-fused heterocyclic cores, especially from an in silico methodological perspective.

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New benzoxazole-based sulphonamide hybrids analogs as potent inhibitors of α-amylase and α-glucosidase: Synthesis and in vitro evaluation along with in silico study

Khan

Rehman

Nawaz

et al. 2022

Arabian Journal of Chemistry

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Molecular docking and dynamic simulations of benzimidazoles with beta-tubulins

Cited by 16 publications

References 14 publications

Insights from the molecular docking and simulation analysis of P38 MAPK phytochemical inhibitor complexes

Insights from the molecular docking and simulation analysis of P38 MAPK phytochemical inhibitor complexes

Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach

New benzoxazole-based sulphonamide hybrids analogs as potent inhibitors of α-amylase and α-glucosidase: Synthesis and in vitro evaluation along with in silico study

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