New thiazolyl‐pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents. Issue 5 (18th March 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 5(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-18
• Subjects: antibacterial activity -- antifungal activity -- antiprotozoal activity -- chalcone -- pyrazoline; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201900351
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: 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 IC50 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 EC50 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. Abstract : A new series of N ‐substituted thiazolyl‐pyrazoline hybrids 6/9a–g was synthetized and screened for antimicrobial and antiprotozoal activity. N ‐3, 5‐Dichlorophenyl pyrazolines 9e –g are the most active compounds of the series against C. neoformans, with low cytotoxic effects toward erythrocytes. N ‐Formyl pyrazolines 7a, 7c, and 7g showed inhibitory activity against S. aureus and N. gonorrhoeae, and thiazolyl‐pyrazolines 9g, 8f, and 7c displayed high activity against P. falciparum, L. panamensis, and T. cruzi .