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-trimeth… Show more
“…The unique structure of quinoline contributes to its interaction with biological systems, leading to its use in medicinal chemistry [7,8]. Quinoline and its derivatives have been employed in the synthesis of drugs with antimalarial [9,10], antitubercular [11,12], antitumor [13,14], antibacterial, and antifungal activities [15,16]. The nitrogen atom in the quinoline ring can serve as a coordination center for metal ions, a property exploited in many aspects of coordination chemistry [17,18].…”
The title compound 1-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl) quinolin-1-ium bromide was obtained in good yield by a facile one-pot, one-step synthetic procedure involving quinoline and an aromatic α-bromo ketone. The product was isolated using hot recrystallization from acetone/acetonitrile solution and characterized using powder and single-crystal XRD, 1D and 2D NMR, DSC, FT-IR, and HRMS analyses.
“…Moreover, compound II was the most potent derivative of the isatin–quinoline hybrids that we reported and assessed formerly for their antimycobacterial activity. [ 22 ] Its MIC equals 0.06 µg/mL, which is considered an excellent hit to be further optimized.…”
In an effort to support the global fight against tuberculosis (TB), which is widely recognized as the most lethal infectious disease worldwide, we present the design and synthesis of new benzo[b]thiophene‐based hybrids as promising candidates for the management of multidrug‐resistant (MDR)/extensively drug‐resistant (XDR) Mycobacterium tuberculosis. The isatin motif was incorporated into the target hybrids as it represents a privileged scaffold in antitubercular drug discovery. Since lipophilicity plays a pivotal role in the anti‐TB agents' activity, the lipophilicity of the target hybrids was manipulated via the development of two series of N‐1 methyl and N‐1 benzyl substituted isatins (6a–h and 9a–h, respectively). Screening of the target hybrids was first performed against drug‐sensitive M. tuberculosis (ATCC 25177). The structure–activity relationship outputs highlighted that incorporation of 3‐unsubstituted benzo[b]thiophene and 5‐methoxy isatin moieties was favorable for the antimycobacterial activity. Thereafter, the most potent molecules (6b–h, 9c–e, and 9h) were evaluated against the resistant strains MDR‐TB (ATCC 35822) as well as against XDR‐TB (RCMB 2674) where they displayed promising activity. To evaluate the safety of the target hybrids, an sulforhodamine B assay was conducted to determine their possible cytotoxic effects on VERO cells.
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