Synthesis of multi ring-fused imidazo [1,2-a]isoquinoline-based fluorescent scaffold as anti-Herpetic agent

Abstract

Background: Natural product-inspired synthesis is a key incorporation in modern diversity-oriented synthesis to yield biologically novel scaffold. Inspired by b-carboline fused system, we have designed molecules with multi ring fused scaffold by modifying the tricyclic pyrido [3,4-b]indole ring with imidazo[1,2-a]isoquinoline. Methods: A highly convergent approach with new C-N and C-C bond formation to synthesize multiring fused complex scaffold imidazo[1,2-a]isoquinolinies as fluorophores. N-nucleophile-induced ring transformation of 2H-pyran-2-one followed by in situ cis-stilbene-type oxidative photocyclization yielded new C-C bond formation without additional oxidant. The cytotoxicity, effective concentrations, and the mode of action of the synthesized analogs were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),, plaque reduction, time of addition, and reverse transcriptase Polymerase Chain Reaction (PCR). Results: Novel imidazo[1,2-a]isoquinoline analogs were prepared, and the results revealed that trans isomer of cyclopropyl analog (EC 50 35 and 37.5 mg/ml) and trans isomer of citric acid salt of phenyl analog (EC 50 38.2 and 39.8 mg/ml) possess significant anti-Herpes Simplex Virus (HSV) activity with selectivity index of >10. The kinetic study demonstrated that both the analogs inhibited HSV-1F and HSV-2G at 2-4 h postinfection. Finally, western blot and reverse transcriptase PCR assays revealed that both the analogs suppressed viral immediate early transcription. Conclusion: Novel imidazo[1,2-a]isoquinoline analogs were synthesized from pyranone with appropriate amines. Two compounds showed better antiviral profile on HSV-infected Vero cells, compared to the standard drug acyclovir (ACV). Overall, we discovered a promising scaffold to develop a nonnucleoside lead targeting the viral immediate early transcription for the management of HSV infections.

Imidazopyridine Family: Versatile and Promising Heterocyclic Skeletons for Different Applications

“…Although structurally different, imidazopyridines exhibit pharmacological properties quite similar to benzodiazepines [ 37 , 65 , 66 , 67 ]. Compounds containing the imidazopyridine moiety exhibit a diverse array of captivating biological characteristics, including antifungal, antipyretic, antiviral, analgesic, antibacterial, anticancer, antiprotozoal, anti-inflammatory, anticonvulsant, anthelmintic, antitubercular, antiulcer, antiepileptic, hypnotic, and anxiolytic properties [ 18 , 68 , 69 , 70 , 71 , 72 ]. They have also been the subject of investigation as receptor agonists.…”