Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity

Abstract

Twenty-four new hybrid analogues (15-38) containing 7-chloro-4-aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized. Twelve of the new compounds were evaluated against 58 human cancer cell lines by the U.S. National Cancer Institute (NCI). Compounds 25, 30, 31, 36, and 37 showed significant cytostatic activity, with the most outstanding GI 50 values ranging from 0.05 to 0.95 µM. The hybrid compounds (15-38) were also evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. From the obtained results some structure-activity relationships were outlined.

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

“…According to recent papers on N ‐aryl pyrazolines, the introduction of the aryl group at the N ‐1 position of the dihydropyrazole ring leads to biological activity improvement. [ 33,45–48 ] However, chlorophenyl derivatives may enhance potency and binding efficiency compared to their unsubstituted phenyl derivatives. [ 2,49,50 ] In addition, these derivatives show an improvement in metabolic stability and pharmacokinetic profile, as recently demonstrated by Eggert et al, [ 49 ] who identified that the 3,4‐dichloro derivative (IC 50 = 0.08 μM) is more active than the corresponding 4‐chloro (IC 50 = 0.8 μM) and unsubstituted phenyl derivatives (IC 50 > 20 μM) against SMYD2 for the treatment of cancer.…”

“…According to the literature, the 2‐pyrazoline moiety confers interesting biological properties to compounds, including the antifungal activity. [ 18,33,34 ] Compounds 3 , 5a–g , 6a–g , 7a–g , 8a–g , and 9a–g were tested for antifungal properties against two clinically important fungal species, Candida albicans and Cryptococcus neoformans , which are involved in invasive fungal infections in immunocompromised patients, leading to high risk of morbidity and mortality. [ 51–53 ]…”

“…2‐Pyrazolines are important anti‐inflammatory and analgesic agents, and some of them are potent drugs such as metamizol, phenylbutazone, and morazone. [ 29 ] Also, pyrazoline derivatives exhibit pharmacological activities such as antitumor, [ 30 ] antibacterial, [ 31 ] anti‐inflammatory, [ 32 ] antifungal, [ 33 ] and antidepressant activities [ 15 ] (Figure 2). Recent studies have revealed that thiazolyl‐pyrazoline derivatives show potent antifungal, [ 34 ] antibacterial, [ 29 ] and antioxidant [ 35 ] activities, in addition to inhibitory effects on the epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy, [ 36–39 ] among others.…”

Quinolines and Quinolones as Antibacterial, Antifungal, Anti-virulence, Antiviral and Anti-parasitic Agents

“…New hybrid analogues containing 7-chloro-4aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized and evaluated for antifungal activity against C. albicans and C. neoformans (Montoya et al 2016). The compounds displayed stronger activity against C. neoformans with the most active derivative showing MIC 50 values of 15.5 and < 3.9 μg/ml against C. albicans and C. neoformans, respectively.…”

Synthesis of New Oxindoles and Determination of Their Antibacterial Properties

“…Isatin-and pyrazole-based compounds are nowadays a huge nest of research that correlate with the biological activity that they show, such as antitumoral [3][4][5][6], antimicrobial [7][8][9], anti-inflammatory [8], and antimicrobial against multidrug-resistant cells [10], among others [11][12][13][14][15][16]. Previously, we have described different strategies to obtain pyrazole-based compounds and the evaluation of their biological activity as antifungal, antibacterial, and antitumor agents showing that some these pyrazole-derivatives were bioactive as antimicrobials [17][18][19][20][21][22]. Combination of isatin and pyrazole moieties could be a good alternative to trigger a better biological activity into a hybrid structure.…”