Design, synthesis and trypanocidal activity of covalent reversible inhibitors of t...
| Full text | |
| Author(s): |
Quilles Jr, Jose C.
;
Tezuka, Daiane Y.
[1, 2]
;
Lopes, Carla D.
[1, 2]
;
Ribeiro, Fernanda L.
[1]
;
Laughton, Charles A.
[3, 4]
;
de Albuquerque, Sergio
[5]
;
Montanari, Carlos A.
[1]
;
Leitao, Andrei
[1]
Total Authors: 8
|
| Affiliation: | [1] Quilles Jr, Jr., Jose C., Univ Sao Paulo, Sao Carlos Inst Chem IQSC, Med Chem Grp NEQUIMED, Av Trabalhador Sao Carlense 400, BR-13566590 Sao Carlos, SP - Brazil
[2] Univ Sao Paulo, Programa Posgrad Bioengn, Av Trabalhador Sao Carlense 400, Sao Carlos, SP - Brazil
[3] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD - England
[4] Univ Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD - England
[5] Univ Sao Paulo, FCFRP, Lab Parasitol, Ribeirao Preto, SP - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Experimental Parasitology; v. 200, p. 84-91, MAY 2019. |
| Web of Science Citations: | 2 |
| Abstract | |
Cysteine proteases are involved in critical cell processes to the protozoa from Leishmania genus, and their inhibition is a therapeutic alternative to treat the disease. In this work, derivatives of dipeptidyl nitriles acting as reversible covalent inhibitors of cysteine proteases were studied as cytostatic agents. The proteolytic activity inside the living and lysed parasite cells was quantified using a selective substrate for cysteine proteases (Z-FR-MCA) from Leishmania amazonensis and L. infantum. The overall proteolytic activity of intact cells and even cell extracts was only marginally affected at high concentrations, with the observation of cytostatic activity and cell cycle arrest of promastigotes. However, the cytotoxic effects were only observed for infected J774 macrophages, which impaired further analysis of the amastigote infection. Therefore, the proteolytic inhibition in intact L. amazonensis and L. infantum promastigotes had no relationship to the cytostatic activity, which emphasizes that these dipeptidyl nitriles act through another mechanism of action. (AU) | |
| FAPESP's process: | 13/18009-4 - Molecular design, synthesis and trypanocidal activity of cruzain reversible covalent inhibitors |
| Grantee: | Carlos Alberto Montanari |
| Support type: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/07292-0 - Molecular design, trypanocidal and anticancer activities of covalent reversible inhibitors of cysteine proteases |
| Grantee: | José Carlos Quilles Junior |
| Support type: | Scholarships in Brazil - Doctorate |