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One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents. | LitMetric
Pulmonary fibrosis is a life threating disease which requires an immediate treatment and due to the limited medications, this study focused on synthesizing a series of quinoline-based pyrimidodiazepines as a novel antifibrotic hit. The target compounds were synthesized via a one-pot reaction then investigated in a rat model of lung fibrosis induced by bleomycin (BLM). Results revealed significant attenuation of the tested pro-inflammatory cytokines, fibrotic genes and apoptotic markers; however, Bcl-2 was upregulated, indicating a protective effect against fibrosis. Moreover, the molecular docking studies highlighted promising interactions between compounds and and specific amino acids within the protein pockets of caspase-3 (ARG341 and THR177), malondialdehyde (LYS195, LYS118 and ARG188) and TNF-α (SER99 and NME102). Compounds and emerge as promising candidates for further preclinical investigation as pulmonary antifibrotic agents.
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