Identification of novel antitubercular compounds through hybrid virtual screening approach

Muhammad Muddassar; Jae Wan Jang; Hong Seung Gon; Yong Seo Cho; Eunice Eunkyung Kim; Kyo Chang Keum; Taegwon Oh; Sang Nae Cho; Ae Nim Pae

doi:10.1016/j.bmc.2010.07.010

Identification of novel antitubercular compounds through hybrid virtual screening approach

Muhammad Muddassar, Jae Wan Jang, Hong Seung Gon, Yong Seo Cho, Eunice Eunkyung Kim, Kyo Chang Keum, Taegwon Oh, Sang Nae Cho, Ae Nim Pae

Department of Microbiology

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Growing resistance of prevalent antitubercular (antiTB) agents in clinical isolates of Mycobacterium tuberculosis (MTB) provoked an urgent need to discover novel antiTB agents. Enoyl acyl carrier protein (ACP) reductase (InhA) from Mtb is a well known and thoroughly studied as antitubucular therapy target. Here we have reported the discovery of potent antiTB agents through ligand and structure based approaches using computational tools. Initially compounds with more than 0.500 Tanimoto similarity coefficient index using functional class fingerprints (FCFP-4) to the reference chemotype were mined from the chemdiv database. Further, the molecular docking was performed to select the compounds on the basis of their binding energies, binding modes, and tendencies to form reasonable interactions with InhA (PDB ID = 2NSD) protein. Eighty compounds were evaluated for antitubercular activity against H37RV M. tuberculosis strain, out of which one compound showed MIC of 5.70 μM and another showed MIC of 13.85 μM. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents.

Original language	English
Pages (from-to)	6914-6921
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2010.07.010
Publication status	Published - 2010 Sept 15

Bibliographical note

Funding Information:
This work was supported by Korea Functional Proteomic Center, 21C Frontier Program of Korea Ministry of Education, Science and Technology and Grants from Korea Institute of Science and Technology (2E21590).

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmc.2010.07.010

Cite this

@article{32f0a76a43be4c11b7180c3cfbcfb0a2,

title = "Identification of novel antitubercular compounds through hybrid virtual screening approach",

abstract = "Growing resistance of prevalent antitubercular (antiTB) agents in clinical isolates of Mycobacterium tuberculosis (MTB) provoked an urgent need to discover novel antiTB agents. Enoyl acyl carrier protein (ACP) reductase (InhA) from Mtb is a well known and thoroughly studied as antitubucular therapy target. Here we have reported the discovery of potent antiTB agents through ligand and structure based approaches using computational tools. Initially compounds with more than 0.500 Tanimoto similarity coefficient index using functional class fingerprints (FCFP-4) to the reference chemotype were mined from the chemdiv database. Further, the molecular docking was performed to select the compounds on the basis of their binding energies, binding modes, and tendencies to form reasonable interactions with InhA (PDB ID = 2NSD) protein. Eighty compounds were evaluated for antitubercular activity against H37RV M. tuberculosis strain, out of which one compound showed MIC of 5.70 μM and another showed MIC of 13.85 μM. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents.",

author = "Muhammad Muddassar and Jang, {Jae Wan} and Gon, {Hong Seung} and Cho, {Yong Seo} and Kim, {Eunice Eunkyung} and Keum, {Kyo Chang} and Taegwon Oh and Cho, {Sang Nae} and Pae, {Ae Nim}",

note = "Funding Information: This work was supported by Korea Functional Proteomic Center, 21C Frontier Program of Korea Ministry of Education, Science and Technology and Grants from Korea Institute of Science and Technology (2E21590). ",

year = "2010",

month = sep,

day = "15",

doi = "10.1016/j.bmc.2010.07.010",

language = "English",

volume = "18",

pages = "6914--6921",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "18",

}

TY - JOUR

T1 - Identification of novel antitubercular compounds through hybrid virtual screening approach

AU - Muddassar, Muhammad

AU - Jang, Jae Wan

AU - Gon, Hong Seung

AU - Cho, Yong Seo

AU - Kim, Eunice Eunkyung

AU - Keum, Kyo Chang

AU - Oh, Taegwon

AU - Cho, Sang Nae

AU - Pae, Ae Nim

N1 - Funding Information: This work was supported by Korea Functional Proteomic Center, 21C Frontier Program of Korea Ministry of Education, Science and Technology and Grants from Korea Institute of Science and Technology (2E21590).

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Growing resistance of prevalent antitubercular (antiTB) agents in clinical isolates of Mycobacterium tuberculosis (MTB) provoked an urgent need to discover novel antiTB agents. Enoyl acyl carrier protein (ACP) reductase (InhA) from Mtb is a well known and thoroughly studied as antitubucular therapy target. Here we have reported the discovery of potent antiTB agents through ligand and structure based approaches using computational tools. Initially compounds with more than 0.500 Tanimoto similarity coefficient index using functional class fingerprints (FCFP-4) to the reference chemotype were mined from the chemdiv database. Further, the molecular docking was performed to select the compounds on the basis of their binding energies, binding modes, and tendencies to form reasonable interactions with InhA (PDB ID = 2NSD) protein. Eighty compounds were evaluated for antitubercular activity against H37RV M. tuberculosis strain, out of which one compound showed MIC of 5.70 μM and another showed MIC of 13.85 μM. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents.

AB - Growing resistance of prevalent antitubercular (antiTB) agents in clinical isolates of Mycobacterium tuberculosis (MTB) provoked an urgent need to discover novel antiTB agents. Enoyl acyl carrier protein (ACP) reductase (InhA) from Mtb is a well known and thoroughly studied as antitubucular therapy target. Here we have reported the discovery of potent antiTB agents through ligand and structure based approaches using computational tools. Initially compounds with more than 0.500 Tanimoto similarity coefficient index using functional class fingerprints (FCFP-4) to the reference chemotype were mined from the chemdiv database. Further, the molecular docking was performed to select the compounds on the basis of their binding energies, binding modes, and tendencies to form reasonable interactions with InhA (PDB ID = 2NSD) protein. Eighty compounds were evaluated for antitubercular activity against H37RV M. tuberculosis strain, out of which one compound showed MIC of 5.70 μM and another showed MIC of 13.85 μM. We believe that these two new scaffolds might be the good starting point from hit to lead optimization for new antitubercular agents.

UR - http://www.scopus.com/inward/record.url?scp=77956317548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956317548&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2010.07.010

DO - 10.1016/j.bmc.2010.07.010

M3 - Article

C2 - 20727773

AN - SCOPUS:77956317548

SN - 0968-0896

VL - 18

SP - 6914

EP - 6921

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 18

ER -

Identification of novel antitubercular compounds through hybrid virtual screening approach

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this