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

被引:17
作者
Abdelrahman, Mohamed A. A. [1 ]
Almahli, Hadia [2 ]
Al-Warhi, Tarfah [3 ]
Majrashi, Taghreed A. A. [4 ]
Abdel-Aziz, Marwa A. M. [5 ]
Eldehna, Wagdy M. M. [6 ,7 ]
Said, Mohamed A. A. [1 ]
机构
[1] Egyptian Russian Univ, Fac Pharm, Dept Pharmaceut Chem, Badr City 11829, Egypt
[2] Univ Cambridge, Dept Chem, Cambridge CB2, England
[3] Princess Nourah bint Abdulrahman Univ, Coll Sci, Dept Chem, PO, Box 84428, , Riyadh 11671, Riyadh 84428, Saudi Arabia
[4] King Khalid Univ, Coll Pharm, Dept Pharmacognosy, Abha 61441, Saudi Arabia
[5] Al Azhar Univ, Reg Ctr Mycol & Biotechnol, Cairo 11651, Egypt
[6] Kafrelsheikh Univ, Fac Pharm, Dept Pharmaceut Chem, Kafrelsheikh 33516, Egypt
[7] Badr Univ Cairo, Sch Biotechnol, Cairo 11829, Egypt
来源
MOLECULES | 2022年 / 27卷 / 24期
关键词
quinolone; hydrazone; anti-mycobacterial activity; Mycobacterium resistance; ANTITUBERCULOSIS ACTIVITY; BIOLOGICAL EVALUATION; IN-VITRO; DERIVATIVES; DESIGN; INHIBITORS; HYDRAZONES; DISCOVERY; DOCKING; HYBRIDS;
D O I
10.3390/molecules27248807
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g/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 mu g/mL, respectively.
引用
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页数:11
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