Novel potentially antibacterial naphthalimide-derived metronidazoles: Design, synthesis, biological evaluation and supramolecular interactions with DNA, human serum albumin and topoisomerase II

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

“…In 2017, Li, Zhou, and coworkers synthesised novel naphthalimide-derived metronidazoles 112a-g and tested their in vitro antibacterial activities towards Gram-positive and Gram-negative bacteria [65]. The synthesis of hybrids 112 was carried out via the reaction sequence shown in Scheme 21, in which commercially available 4-bromo-1,8-naphthalic anhydride (namely, 6-bromo-1H-benzo[de]isoquinoline-1,3(2H)-dione) (113) was the starting material.…”

“…Among these hybrids, compound 112b (R 1 = R 2 = H; n = 2) proved capable of not only exhibiting effective inhibition towards the growth of both P. vulgaris (MIC = 2 µM), a Gram-negative bacterium that inhabits the intestinal tract of humans and animals, and S. dysenteriae (MIC = 10 µM), a Gram-negative fluoroquinolone-resistant bacterium that can cause shigellosis (bacillary dysentery), but also of rapidly killing the tested strains and to prevent development of bacterial resistance. Interestingly, hybrid 112b also proved capable of intercalating into calf thymus DNA to form a steady supramolecular complex, which might block DNA replication to display the antibacterial activity and being effectively transported by human serum albumin [65].…”

“…The coupling of 117 with 2-methyl-5-nitro-1H-imidazole (64) in DMF in the presence of K 2 CO 3 gave in 64% yield the nitroimidazole derivative 118, which was reduced with NaBH 4 in EtOH at 60 • C for 6 h affording compound 119 in a moderate yield. Finally, target hybrids 112a-g were obtained in 40-60% yield by reaction of 119 with amines 120a-g in DMSO at 90 • C for 4 h under N 2 atmosphere using K 2 CO 3 as base and Cu 2 O as catalyst [65].…”

Researches and applications of nitroimidazole heterocycles in medicinal chemistry

“…合方式与生物的活性位点发生超分子相互作用, 可以 作为人工离子受体、荧光探针、细胞显像剂等来治疗 多种疾病 [75,76] , 近年来用唑类杂环如咪唑、三唑、噻 唑等修饰萘酰亚胺得到的化合物显示出较好的抗菌活 性 [77~79] , 相关研究备受关注 [80,81] . 萘酰亚胺类衍生物 36a (图4)不仅能快速抑制枯草芽孢杆菌(Bacillus subtilis, 0.0020 µmol/mL)和痢疾志贺氏菌(Shigella dysenteriae, 0.010 µmol/mL)的生长, 还可以防止细菌耐药性 的发生, 对萘酰亚胺氨基引入不同的取代基进行探索 发现, 较长的烷基链如十二烷或羟乙基会降低化合物 的抗菌活性 [82] . 然而进一步研究发现, 若将带有较长 烷基链的脂环胺哌嗪引入共轭体系中得到化合物36b 反而对鲍曼不动杆菌(Acinetobacter bauman)显示出较 强的抑制效果(MIC=0.013 μmol/mL), 值得作为潜在的 多靶点抗菌剂进行深入研究 [83] .…”

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

“…Moreover, several reports have also shown that naphthalimide derivatives could effectively inhibit the growth of micro‐organisms and possess vast potential in the treatment of bacterial and fungal infections, further confirming the possibility of naphthalimide utilization in the medical field (Damu et al., ; Zhang & Zhou, ). In particular, naphthalimide‐heterocyclic ring conjugates exhibited better antimicrobial activities against different bacterial strains compared to reference drugs, chloromycin and norfloxacin (Gong, Kishore, Lv, Cai, & Zhou, ; Kang, Gopala, Tangadanchu, Gao, & Zhou, ; Kang et al., ; Lv, Peng, Kishore, & Zhou, ).…”