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Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase

Antibiotic resistance remains a major threat to humans worldwide, owing to the ability of bacteria and fungi to mutate over time, as well as a dramatic decline in the antibiotic pipeline. Plants are widely recognised as sources for various bioactive secondary metabolites that can be developed as a h...

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Main Authors: Abdul Aziz, Ahmad Amzar, Aminudin, Nurul Iman, Abd Hamid, Shafida, Pungot, Noor Hidayah, Hamzah, Nurasyikin
Format: Article
Language:English
English
Published: Malaysian Institute of Chemistry (Institut Kimia Malaysia) 2023
Subjects:
QD Chemistry
Online Access:http://irep.iium.edu.my/106834/8/106834_Molecular%20docking%20and%20ADME%20profiles%20of%20%CE%B2-Carboline.pdf
http://irep.iium.edu.my/106834/7/106834_Molecular%20docking%20and%20ADME%20profiles%20of%20%CE%B2-Carboline_SCOPUS.pdf
http://irep.iium.edu.my/106834/
https://ikm.org.my/publications/malaysian-journal-of-chemistry/view-abstract.php?abs=J0044-d167501
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spelling my.iium.irep.1068342023-10-11T07:37:24Z http://irep.iium.edu.my/106834/ Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase Abdul Aziz, Ahmad Amzar Aminudin, Nurul Iman Abd Hamid, Shafida Pungot, Noor Hidayah Hamzah, Nurasyikin QD Chemistry Antibiotic resistance remains a major threat to humans worldwide, owing to the ability of bacteria and fungi to mutate over time, as well as a dramatic decline in the antibiotic pipeline. Plants are widely recognised as sources for various bioactive secondary metabolites that can be developed as a hit compound for further antibiotic discoveries. β-Carboline has been recognised as one of the hit compounds exhibiting various biological activities including antibacterial properties. However, the optimisation and development of the hit compound always hampered by long and expensive procedures. The in-silico approaches involving molecular docking and ADME profiling can be expedite the process. Herein, an in-house library of β-carboline and its 19 analogues were virtually screened to evaluate their antibiotic activities and drug-likeness properties using molecular docking and ADME profiling respectively. Docking studies showed that all 19 β-carboline analogues strongly bound to the target protein (-6.8 to -9.4 kcal/mol) except 1o (-6.7 kcal/mol), which exhibited binding energy comparable to the reference drug, novobiocin (-6.8 kcal/mol). Of these, derivatives 1l bound the strongest (-9.4 kcal/mol) mainly due to the hydrogen bond interactions that occurred between the carboxylic acid moiety with Val71. ADME profiling showed that all β-carboline analogues demonstrated favourable drug-likeness properties and obey the Lipinski Rule of 5 (Ro5). The analogues 1l showed only one inhibition on CYP2D6 suggesting less toxicity properties. Thus, through this work, the derivatives of β-carboline, especially 1l, may serve as hit compound for future development of finding effective antibiotic agent. Malaysian Institute of Chemistry (Institut Kimia Malaysia) 2023-06-29 Article PeerReviewed application/pdf en http://irep.iium.edu.my/106834/8/106834_Molecular%20docking%20and%20ADME%20profiles%20of%20%CE%B2-Carboline.pdf application/pdf en http://irep.iium.edu.my/106834/7/106834_Molecular%20docking%20and%20ADME%20profiles%20of%20%CE%B2-Carboline_SCOPUS.pdf Abdul Aziz, Ahmad Amzar and Aminudin, Nurul Iman and Abd Hamid, Shafida and Pungot, Noor Hidayah and Hamzah, Nurasyikin (2023) Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase. Malaysian Journal of Chemistry, 25 (3). pp. 415-424. ISSN 1511-2292 E-ISSN 2550-1658 https://ikm.org.my/publications/malaysian-journal-of-chemistry/view-abstract.php?abs=J0044-d167501 10.55373/mjchem.v25i3.415
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
English
topic QD Chemistry
spellingShingle QD Chemistry
Abdul Aziz, Ahmad Amzar
Aminudin, Nurul Iman
Abd Hamid, Shafida
Pungot, Noor Hidayah
Hamzah, Nurasyikin
Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase
description Antibiotic resistance remains a major threat to humans worldwide, owing to the ability of bacteria and fungi to mutate over time, as well as a dramatic decline in the antibiotic pipeline. Plants are widely recognised as sources for various bioactive secondary metabolites that can be developed as a hit compound for further antibiotic discoveries. β-Carboline has been recognised as one of the hit compounds exhibiting various biological activities including antibacterial properties. However, the optimisation and development of the hit compound always hampered by long and expensive procedures. The in-silico approaches involving molecular docking and ADME profiling can be expedite the process. Herein, an in-house library of β-carboline and its 19 analogues were virtually screened to evaluate their antibiotic activities and drug-likeness properties using molecular docking and ADME profiling respectively. Docking studies showed that all 19 β-carboline analogues strongly bound to the target protein (-6.8 to -9.4 kcal/mol) except 1o (-6.7 kcal/mol), which exhibited binding energy comparable to the reference drug, novobiocin (-6.8 kcal/mol). Of these, derivatives 1l bound the strongest (-9.4 kcal/mol) mainly due to the hydrogen bond interactions that occurred between the carboxylic acid moiety with Val71. ADME profiling showed that all β-carboline analogues demonstrated favourable drug-likeness properties and obey the Lipinski Rule of 5 (Ro5). The analogues 1l showed only one inhibition on CYP2D6 suggesting less toxicity properties. Thus, through this work, the derivatives of β-carboline, especially 1l, may serve as hit compound for future development of finding effective antibiotic agent.
format Article
author Abdul Aziz, Ahmad Amzar
Aminudin, Nurul Iman
Abd Hamid, Shafida
Pungot, Noor Hidayah
Hamzah, Nurasyikin
author_facet Abdul Aziz, Ahmad Amzar
Aminudin, Nurul Iman
Abd Hamid, Shafida
Pungot, Noor Hidayah
Hamzah, Nurasyikin
author_sort Abdul Aziz, Ahmad Amzar
title Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase
title_short Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase
title_full Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase
title_fullStr Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase
title_full_unstemmed Molecular docking and ADME profiles of β-Carboline analogues as potential antibiotic agents targeting DNA gyrase
title_sort molecular docking and adme profiles of β-carboline analogues as potential antibiotic agents targeting dna gyrase
publisher Malaysian Institute of Chemistry (Institut Kimia Malaysia)
publishDate 2023
url http://irep.iium.edu.my/106834/8/106834_Molecular%20docking%20and%20ADME%20profiles%20of%20%CE%B2-Carboline.pdf
http://irep.iium.edu.my/106834/7/106834_Molecular%20docking%20and%20ADME%20profiles%20of%20%CE%B2-Carboline_SCOPUS.pdf
http://irep.iium.edu.my/106834/
https://ikm.org.my/publications/malaysian-journal-of-chemistry/view-abstract.php?abs=J0044-d167501
_version_ 1781777350981058560
score 13.211869

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