New thiazolyl‐pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

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 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 methicillinsusceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycinintermediate 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. K E Y W O R D S antibacterial activity, antifungal activity, antiprotozoal activity, chalcone, pyrazoline

Coumaro-chalcones synthesized under solvent-free conditions as potential agents against malaria, leishmania and trypanosomiasis

“…Cytotoxicity results were expressed as lethal concentration 50 (LC 50 ) corresponding to the concentration necessary to eliminate 50% of cells. The degree of toxicity was established according to the LC 50 value using the following scale: compounds with LC 50 < 100 μM were considered as potentially cytotoxic, with 100 ≤ LC 50 < 200 μM as mildly cytotoxic, and with LC 50 ≥ 200 μM as noncytotoxic ( Cuartas et al., 2020 ).…”

“…The effective media concentration was defined as the concentration of the compound that decreases 50% of intracellular parasites. Compounds with EC 50 ≤ 25 μM were considered highly active ( Cuartas et al., 2020 ).…”

“…The degree of toxicity was established according to the LC 50 value using the following scale: compounds with LC 50 < 100 μM were considered as potentially cytotoxic, with 100 LC 50 < 200 μM as mildly cytotoxic, and with LC 50 ! 200 μM as noncytotoxic (Cuartas et al, 2020).…”

Eugenol carbonate activity against Plasmodium falciparum, Leishmania braziliensis, and Trypanosoma cruzi

“…After 72 h of incubation, 100 μl of chlorophenol red‐β‐D‐galactopyranoside (CPRG) at 100 µM and 0.1% Nonidet P‐40 were added, and after 3 h of incubation, absorbance was read at 570 nm (Varioskan; Thermo Fisher Scientific). [ 39 ] Infected cells exposed to BNZ were used as a control for trypanocidal activity (positive control), while infected and untreated cells were used as a control for infection (negative control). The nonspecific absorbance was corrected by subtracting the absorbances of the blank solution.…”

Pyrazol(in)e Derivatives of Curcumin Analogs As a New Class of Anti- Trypanosoma Cruzi Agents

“…In two recent publications, Insuasty et al reported the synthesis and antitrypanosomal activity of novel caffeine-based pyrazolines [25] and thiazolyl-pyrazoline derivatives bearing nitrogen mustard (Fig. 1) [26]. All the aforementioned evidence promted us to design and synthesize substituted pyrazole/2-pyrazolines generated from curcuminoid precursors aiming to combine these two bioactive structures into one molecule, thus further improving the promising activities of curcuminoids.…”