TY - JOUR
T1 - Benzoic acid derivatives with trypanocidal activity
T2 - Enzymatic analysis and molecular docking studies toward trans-sialidase
AU - Kashif, Muhammad
AU - Moreno-Herrera, Antonio
AU - Villalobos-Rocha, Juan Carlos
AU - Nogueda-Torres, Benjamín
AU - Pérez-Villanueva, Jaime
AU - Rodríguez-Villar, Karen
AU - Medina-Franco, José Luis
AU - De Andrade, Peterson
AU - Carvalho, Ivone
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/11
Y1 - 2017/11
N2 - Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0.15 μM on the NINOA strain, and LC50 < 0.22 μM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).
AB - Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0.15 μM on the NINOA strain, and LC50 < 0.22 μM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).
KW - Benzoic acid
KW - Chagas disease
KW - Docking
KW - Inhibitors
KW - Trans-sialidase
UR - http://www.scopus.com/inward/record.url?scp=85033782334&partnerID=8YFLogxK
U2 - 10.3390/molecules22111863
DO - 10.3390/molecules22111863
M3 - Artículo
C2 - 29084172
SN - 1420-3049
VL - 22
JO - Molecules
JF - Molecules
IS - 11
M1 - 1863
ER -