Discovery of 2,3-dihydro-1 H -pyrrolo[3,4- b ]quinolin-1-one derivatives as possible antileishmanial agents.

Autor: Seth A; Molecular Microbiology and Immunology Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India susantakar@cdri.res.in.; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India., Ghoshal A; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.; Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India ajayk.srivastava@cdri.res.in., Dewaker V; Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India ajayk.srivastava@cdri.res.in., Rani A; Molecular Microbiology and Immunology Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India susantakar@cdri.res.in.; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India., Singh SP; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.; Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India ajayk.srivastava@cdri.res.in., Dutta M; Molecular Microbiology and Immunology Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India susantakar@cdri.res.in.; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India., Katiyar S; Molecular Microbiology and Immunology Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India susantakar@cdri.res.in., Singh SK; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.; Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India., Rashid M; Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India., Wahajuddin M; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.; Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India., Kar S; Molecular Microbiology and Immunology Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India susantakar@cdri.res.in.; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India., Srivastava AK; Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.; Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India ajayk.srivastava@cdri.res.in.
Jazyk: angličtina
Zdroj: RSC medicinal chemistry [RSC Med Chem] 2022 May 11; Vol. 13 (6), pp. 746-760. Date of Electronic Publication: 2022 May 11 (Print Publication: 2022).
DOI: 10.1039/d2md00078d
Abstrakt: A series of uniquely functionalized 2,3,-dihydro-1 H -pyyrolo[3,4- b ]quinolin-1-one derivatives were synthesized in one to two steps by utilizing a post-Ugi modification strategy and were evaluated for antileishmanial efficacy against visceral leishmaniasis (VL). Among the library compounds, compound 5m exhibited potential in vitro antileishmanial activity (CC 50 = 65.11 μM, SI = 7.79, anti-amastigote IC 50 = 8.36 μM). In vivo antileishmanial evaluation of 5m demonstrated 56.2% inhibition in liver and 61.1% inhibition in spleen parasite burden in infected Balb/c mice (12.5 mg kg -1 , i.p.). In vitro pharmacokinetic study ascertained the stability of 5m in both simulated gastric fluid and simulated intestinal fluid. All the active compounds passed the PAINS filter and showed no toxicity in in silico predictions.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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