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New thiazolyl‐pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents
Author(s) -
Cuartas Viviana,
Robledo Sara M.,
Vélez Iván D.,
Crespo María del Pilar,
Sortino Maximiliano,
Zacchino Susana,
Nogueras Manuel,
Cobo Justo,
Upegui Yulieth,
Pineda Tatiana,
Yepes Lina,
Insuasty Braulio
Publication year - 2020
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201900351
Subject(s) - antiprotozoal , chemistry , antimicrobial , pyrazoline , thiazole , staphylococcus aureus , chalcone , stereochemistry , minimum inhibitory concentration , cryptococcus neoformans , bacillus cereus , microbiology and biotechnology , biochemistry , organic chemistry , bacteria , biology , in vitro , genetics
A new series of N ‐substituted pyrazoline derivatives 6a–g , 7a–g , 8a–g , and 9a–g was synthetized by reaction of hydrazine derivatives and chalcone–thiazole hybrids bearing nitrogen mustard 5a–g . The chalcones 5a–g were obtained by Claisen–Schmidt condensation of thiazole‐2‐nitrogen mustard 3 and selected acetophenones 4a–g . These new compounds 6/7/8/9a–g were screened for their antifungal activity against Cryptococcus neoformans , with IC 50 values of 3.9–7.8 µg/ml for the N ‐3,5‐dichlorophenyl pyrazolines 9e – g . Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N ‐acetyl ( 6a,b ) and N ‐formyl pyrazolines ( 7a , 7b , 7c , and 7g ) showed inhibitory activity against methicillin‐susceptible Staphylococcus aureus , methicillin‐resistant S. aureus , and vancomycin‐intermediate S. aureus , with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl‐pyrazolines 9g , 8f , and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis , and Trypanosoma cruzi , with EC 50 values of 11.80, 6.46, and 4.98 μM, respectively, and with 7c being approximately 2.6‐fold more potent than benznidazole with a selectivity index of 1.61 on U‐937 human cells, showing promising potential as a novel antitrypanosomal agent.