Journal
MOLECULES
Volume 26, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/molecules26164828
Keywords
acylhydrazone; homologation; anti-inflammatory; analgesic; pain; in silico drug-like
Funding
- INCT-INOFAR (BR) [573.564/2008-6, E-26/170.020/2008]
- CAPES (BR) [001]
- CNPq [573.564/2008-6]
- FAPERJ [E-26/170.020/2008, E-26/202.676/2019]
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Acylhydrazones are important in the design of new bioactive compounds. In this study, cyclopentyl, cyclobutyl, and cyclopropylacylhydrazones were designed, synthesized, and evaluated for their anti-inflammatory and analgesic effects. Compounds 4a and 4e were identified as new analgesic lead-candidates with excellent in silico drug-like profiles.
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.
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