TY - JOUR
T1 - Converging thiolactone and quinoline scaffolds
T2 - New potential antitubercular conjugates
AU - Azeeza, Shaik
AU - Malik, M. Shaheer
AU - Alsimaree, Abdulrahman A.
AU - Khan, Inshad Ali
AU - Abdullah, Sheikh Tasduq
AU - Jamal, Qazi Mohammad Sajid
AU - Alzahrani, Abdullah Y.A.
AU - Moussa, Ziad
AU - Asghar, Basim H.
AU - Ahmed, Saleh A.
AU - Kamal, Ahmed
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2024/3/15
Y1 - 2024/3/15
N2 - Tuberculosis infections pose a serious challenge, particularly because of the emergence of drug resistant mycobacterial strains, highlighting the need of development of new drugs. We report twenty-four new compounds that are designed and synthesized by converging thiolactone and quinoline scaffolds as potential antitubercular entities. Bacterial assay demonstrated one of the conjugates, 4f to be a highly potent molecule with minimum inhibitory concentration (MIC) value of 0.5 μg/mL, comparable to first line drugs. Remarkably, the conjugate 4f demonstrated similar potency against rifampicin and multidrug resistant mycobacterial strains while exhibiting little toxicity against normal cells. In vivo studies demonstrated the promising potential of the conjugate for further development. Finally, a molecular docking study was conducted on four different targets to elucidate the plausible mechanism of action.
AB - Tuberculosis infections pose a serious challenge, particularly because of the emergence of drug resistant mycobacterial strains, highlighting the need of development of new drugs. We report twenty-four new compounds that are designed and synthesized by converging thiolactone and quinoline scaffolds as potential antitubercular entities. Bacterial assay demonstrated one of the conjugates, 4f to be a highly potent molecule with minimum inhibitory concentration (MIC) value of 0.5 μg/mL, comparable to first line drugs. Remarkably, the conjugate 4f demonstrated similar potency against rifampicin and multidrug resistant mycobacterial strains while exhibiting little toxicity against normal cells. In vivo studies demonstrated the promising potential of the conjugate for further development. Finally, a molecular docking study was conducted on four different targets to elucidate the plausible mechanism of action.
KW - Antibacterial agents
KW - Antitubercular
KW - Cytotoxicity
KW - In vivo studies
KW - Molecular docking simulation
KW - Quinolylpiperazines
KW - Thiolactomycin
UR - http://www.scopus.com/inward/record.url?scp=85179123721&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85179123721&partnerID=8YFLogxK
U2 - 10.1016/j.molstruc.2023.137255
DO - 10.1016/j.molstruc.2023.137255
M3 - Article
AN - SCOPUS:85179123721
SN - 0022-2860
VL - 1300
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
M1 - 137255
ER -
