Microwave‐Assisted Highly Efficient Route to 4‐Aminoquinoline‐Phthalimide Conjugates: Synthesis and Anti‐Tubercular Evaluation

Abstract

Microwave assisted synthesis of 4-aminoquinoline-phthalimides was carried out in order to probe their anti-tubercular potential. Different conditions were screened both under conventional and microwave heating and the best results were obtained by microwave heating in DMSO at 160 o C for 2 min affording the desired 4-aminoquinoline-phthalimides in quantitative yields. Anti-tubercular evaluation against mc 2 6230 strain of Mycobacterium tuberculosis revealed 3 e, having an octyl chain length as spacer, to be the most potent of the synthesized compounds exhibiting MIC 99 of 13.7 mM.

Design and synthesis of 4-Aminoquinoline-isoindoline-dione-isoniazid triads as potential anti-mycobacterials

“…Relating the activity and cytotoxicity data of currently synthesized compounds (6e, 8e, 11) with our earlier report (I-IV) [28][29][30][31], the introduction of INH at C-5 of isoindoline ring not only improved anti-mycobacterial activity but also resulted in the reduction of cytotoxicity (Figure 2). The general anti-TB SAR/cytotoxicity of the synthesized series of 4-aminoquinolineisoindoline-isoniazid triads is elucidated in Figure 3.…”

“…Recently, we introduced a functionalized isoindoline-1,3-diones into the alkyl chain of 4aminoquinolines to access their anti-mycobacterial potency. The compounds were promising candidates with a MIC of 5.9-6.25 µg/mL against the mc 2 6230 strain of M. tuberculosis (Figure 2) [28][29]. Motivated by these results and in continuation [30], the present work is a logical extension and involves the synthesis and anti-mycobacterial evaluation of 4aminoquinoline-isoniazid hybrids linked via isoindoline-1,3-diones.…”

Synthesis, anti-mycobacterial and cytotoxic evaluation of substituted isoindoline-1,3-dione-4-aminoquinolines coupled via alkyl/amide linkers

“…1) with secondary amine on isoindoline-1,3-dione ring, not only improved the anti-TB activity but also reduced their cytotoxicity, which were in the range of 5.03-20.92 mg mL À1 . 26 Introduction of a piperidine ring at the C-4/C-5 a The MIC expressed in mg mL À1 were determined using the microdilution method in broth medium; m, n are alkyl chain length (Schemes 1-3).…”

“…1). 26 In continuation of our efforts, 27 we present herein the synthesis and anti-mycobacterial activities of secondary amino-substituted isoindoline-1,3-dione-4-aminoquinolines. The spacer length between two pharmacophores as well as the secondary amine functionality at the C4/C5 position of isoindoline-1,3-dione was meticulously altered for analysing the structure-activity relationship (SAR).…”

Design, synthesis, anti‐mycobacterial and cytotoxic evaluation of C‐4 functionalized 1,8‐naphthalimide‐heterocyclic hydrazide conjugates

“…In the field of TB research and development, due to an increase in the number of MDR/TDR strains, novel medical strategies focussing on the introduction of new molecules, repurposing and derivatization of present drugs have been developed. In continuation (Rani, Viljoen, Sumanjit, Kremer, & Kumar, ; Shalini, Viljoen, & Kremer, ; Singh, Viljoen, Kremer, & Kumar, , ), the present work describes design and synthesis of a library of hybrids of 1,8‐naphthalimide with three types of hydrazides viz INH, nicotinic hydrazide and pyrazine‐2‐carbohydrazide in order to check their anti‐mycobacterial potency. Our rationale considered two major factors in order to have a potent anti‐TB entity and is based on synergistic effect by two pharmacophoric units: (a) clubbing naphthalimide with a nitrogen heterocycle (hydrazides of nicotinic acid, isonicotinic acid, pyrazinecarboxylic acid) that eventually brings possibility of improving its antibacterial property and (b) protection of NH 2 group of hydrazides by introducing naphthalimide ring so as to evade N ‐acetylation (Figure ).…”