Design and Synthesis In Silico Drug-like Prediction and Pharmacological Evaluation of Cyclopolymethylenic Homologous of LASSBio-1514

Molecules

Aline Cavalcanti de Queiroz¹  Magna Suzana Alexandre-Moreira¹  Walfrido Bispo Júnior¹  Tiago Fernandes da Silva²  Lidia Moreira Lima²  Cristiane Aparecida-Silva²  Eliezer J. Barreiro²  Gisele Zapata-Sudo³  Carlos Eduardo da Silva Monteiro³ 

[1] LaFI—Laboratório de Farmacologia e Imunidade, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió 57072-900, AL, Brazil;Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio^®), Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, CCS, Cidade Universitária, Rio de Janeiro21941-971, RJ, Brazil;Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil;

关键词: acylhydrazone;    homologation;    anti-inflammatory;    analgesic;    pain;    in silico drug-like;   

DOI  :  10.3390/molecules26164828

来源: DOAJ

【 摘 要 】

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a–e), cyclobutyl- (3a–e), and cyclopropylacylhydrazones (4a–e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.

【 授权许可】

Unknown