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Development of Novel Isatin-Tethered Quinolines as Anti-Tubercular Agents against Multi and Extensively Drug-Resistant Mycobacterium tuberculosis.

Published version
Peer-reviewed

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Authors

Abdelrahman, Mohamed A  ORCID logo  https://orcid.org/0000-0002-4205-0538
Almahli, Hadia 
Al-Warhi, Tarfah 
Majrashi, Taghreed A 
Abdel-Aziz, Marwa M 

Abstract

We describe the design and synthesis of two isatin-tethered quinolines series (Q6a-h and Q8a-h), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound IV disclosed the highest potency with MIC value equal to 6.24 µg/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound IV with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules Q6a-h. Thereafter, the isatin motif was N-substituted with either a methyl or benzyl group to furnish the second series Q8a-h. All of the designed quinoilne-isatin conjugates Q6a-h and Q8a-h were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the N-benzyl-bearing compound Q8b possessed the best activities against the examined M. tuberculosis strains with MICs equal 0.06, 0.24, and 1.95 µg/mL, respectively.

Description

Peer reviewed: True

Keywords

Article, quinolone, hydrazone, anti-mycobacterial activity, Mycobacterium resistance

Journal Title

Molecules

Conference Name

Journal ISSN

1420-3049
1420-3049

Volume Title

Publisher

MDPI AG
Sponsorship
Princess Nourah bint Abdulrahman University (PNURSP2022R25)
King Khalid University (RGP.1/346/43)