Molecular Modeling and Chemical Synthesis of New Safrol Oxime Ether Derivatives

• Published in: Journal of the Brazilian Chemical Society Vol. 32; no. 7; pp. 1476 - 1490
• Main Authors: Silva, Mariana G. R., Veloso, Marcia P., Chagas, Thaynan A. B., Cordeiro, Mirian M., Alves, Levy B., Monti, Paloma A. G., Souza, Ruth V.
• Format: Journal Article
• Language: English; Portuguese
• Published: SAO PAULO Soc Brasileira Quimica 01.07.2021; Sociedade Brasileira de Química
• Subjects: Chemistry; CHEMISTRY, MULTIDISCIPLINARY; Physical Sciences; Science & Technology; CYSTEINE PROTEASE; SPECIFICITY; NATURAL-PRODUCTS; KINASE; safrol oxime ether; CRK3; rCPB2; leishmaniasis; IDENTIFICATION; LEISHMANIA-MEXICANA; VIRULENCE FACTORS; molecular modeling; 8; INHIBITORS; rCPB2.8
• ISSN: 0103-5053; 1678-4790; 1678-4790
• DOI: 10.21577/0103-5053.20210047

Leishmaniasis, a neglected tropical disease with a high worldwide incidence, is considered a public health issue in Minas Gerais and Brazil, with a high degree of morbidity, not to mention the lack of therapeutic arsenal. The cysteine protease (rCPB2.8) and cyclin dependent kinase (CRK3), important enzymes for the parasite's feasibility, were the targets chosen for investigation of the new drugs. The following study aimed to analyze several oximic derivatives starting from safrol, which can present an affinity profile for selected molecular targets using tools from molecular modeling and bioinformatics, planning and synthesis of brand new substances being tested for leishmanicidal drugs. The study allowed to verify that three oximic derivatives (5a, 5f and 5h) presented high affinity for the CRK3 enzyme, and that the compounds 5c and 5g presented good interaction by the amino acids of the catalytic site of the rCPB2.8 enzyme with atomic distances capable of generating covalent bonds, which are essential for enzyme inhibitory activity.