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

Abstract

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.

• Authors: Lidia Moreira Lima, Tiago Fernandes da Silva, Carlos Eduardo da Silva Monteiro, Cristiane Aparecida-Silva, Walfrido Bispo Júnior, Aline Cavalcanti de Queiroz, Magna Suzana Alexandre-Moreira, Gisele Zapata-Sudo, Eliezer J Barreiro
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 26 Issue 16 (Aug 10 2021) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 34443416 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Anti-Inflammatory Agents
• Hydrazones
• Pharmaceutical Preparations
• Aspirin
• Indomethacin

Topics

• Analgesics (pharmacology)
• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Aspirin (pharmacology)
• Caco-2 Cells
• Computer Simulation
• Drug Design
• Humans
• Hydrazones (chemical synthesis, chemistry, pharmacology)
• Hyperalgesia (pathology)
• Indomethacin (pharmacology)
• Male
• Mice
• Molecular Conformation
• Molecular Weight
• Pharmaceutical Preparations (chemical synthesis, chemistry)
• Rats, Wistar
• Rats