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In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents

With an alarming increase in the number of cancer patients and a variety of tumors, it is high time for intensive investigation on more efficient and potent anti-tumor agents. Though numerous agents have enriched the literature, still there exist challenges, with the availability of different target...

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Autores principales: Dasmahapatra, Upala, Kumar, Chitluri Kiran, Das, Soumyadip, Subramanian, Prathima Thimma, Murali, Poornimaa, Isaac, Arnold Emerson, Ramanathan, Karuppasamy, MM, Balamurali, Chanda, Kaushik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9566731/
https://www.ncbi.nlm.nih.gov/pubmed/36247684
http://dx.doi.org/10.3389/fchem.2022.991369
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author Dasmahapatra, Upala
Kumar, Chitluri Kiran
Das, Soumyadip
Subramanian, Prathima Thimma
Murali, Poornimaa
Isaac, Arnold Emerson
Ramanathan, Karuppasamy
MM, Balamurali
Chanda, Kaushik
author_facet Dasmahapatra, Upala
Kumar, Chitluri Kiran
Das, Soumyadip
Subramanian, Prathima Thimma
Murali, Poornimaa
Isaac, Arnold Emerson
Ramanathan, Karuppasamy
MM, Balamurali
Chanda, Kaushik
author_sort Dasmahapatra, Upala
collection PubMed
description With an alarming increase in the number of cancer patients and a variety of tumors, it is high time for intensive investigation on more efficient and potent anti-tumor agents. Though numerous agents have enriched the literature, still there exist challenges, with the availability of different targets and possible cross-reactivity. Herein we have chosen the phosphoinositide 3-kinase (PI3K) as the target of interest and investigated the potential of pyrido fused imidazo[4,5-c]quinoline derivatives to bind strongly to the active site, thereby inhibiting the progression of various types of tumors. The AutoDock, Glide and the Prime-MM/GBSA analysis are used to execute the molecular docking investigation and validation for the designed compounds. The anti-tumor property evaluations were carried out by using PASS algorithm. Based on the GLIDE score, the binding affinity of the designed molecules towards the target PI3K was evaluated. The energetics associated with static interactions revealed 1j as the most potential candidate and the dynamic investigations including RMSD, RMSF, Rg, SASA and hydrogen bonding also supported the same through relative stabilization induced through ligand interactions. Subsequently, the binding free energy of the Wortmannin and 1j complex calculated using MM-PBSA analysis. Further evaluations with PASS prediction algorithm also supported the above results. The studies reveal that there is evidence for considering appropriate pyrido fused imidazo[4,5-c]quinoline compounds as potential anti-tumor agents.
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spelling pubmed-95667312022-10-15 In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents Dasmahapatra, Upala Kumar, Chitluri Kiran Das, Soumyadip Subramanian, Prathima Thimma Murali, Poornimaa Isaac, Arnold Emerson Ramanathan, Karuppasamy MM, Balamurali Chanda, Kaushik Front Chem Chemistry With an alarming increase in the number of cancer patients and a variety of tumors, it is high time for intensive investigation on more efficient and potent anti-tumor agents. Though numerous agents have enriched the literature, still there exist challenges, with the availability of different targets and possible cross-reactivity. Herein we have chosen the phosphoinositide 3-kinase (PI3K) as the target of interest and investigated the potential of pyrido fused imidazo[4,5-c]quinoline derivatives to bind strongly to the active site, thereby inhibiting the progression of various types of tumors. The AutoDock, Glide and the Prime-MM/GBSA analysis are used to execute the molecular docking investigation and validation for the designed compounds. The anti-tumor property evaluations were carried out by using PASS algorithm. Based on the GLIDE score, the binding affinity of the designed molecules towards the target PI3K was evaluated. The energetics associated with static interactions revealed 1j as the most potential candidate and the dynamic investigations including RMSD, RMSF, Rg, SASA and hydrogen bonding also supported the same through relative stabilization induced through ligand interactions. Subsequently, the binding free energy of the Wortmannin and 1j complex calculated using MM-PBSA analysis. Further evaluations with PASS prediction algorithm also supported the above results. The studies reveal that there is evidence for considering appropriate pyrido fused imidazo[4,5-c]quinoline compounds as potential anti-tumor agents. Frontiers Media S.A. 2022-09-30 /pmc/articles/PMC9566731/ /pubmed/36247684 http://dx.doi.org/10.3389/fchem.2022.991369 Text en Copyright © 2022 Dasmahapatra, Kumar, Das, Subramanian, Murali, Isaac, Ramanathan, MM and Chanda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Dasmahapatra, Upala
Kumar, Chitluri Kiran
Das, Soumyadip
Subramanian, Prathima Thimma
Murali, Poornimaa
Isaac, Arnold Emerson
Ramanathan, Karuppasamy
MM, Balamurali
Chanda, Kaushik
In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
title In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
title_full In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
title_fullStr In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
title_full_unstemmed In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
title_short In-silico molecular modelling, MM/GBSA binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
title_sort in-silico molecular modelling, mm/gbsa binding free energy and molecular dynamics simulation study of novel pyrido fused imidazo[4,5-c]quinolines as potential anti-tumor agents
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9566731/
https://www.ncbi.nlm.nih.gov/pubmed/36247684
http://dx.doi.org/10.3389/fchem.2022.991369
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