Synthesis of novel quinoline-based 4,5-dihydro-1H-pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.
A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI50values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC50values ranging from 2.6 to > 100 μM (1.2 to > 51.7 μg/mL), for chalcones 8a,d and pyrazolines 10c,d. All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against Candida albicans, chalcones 8a and 8e showed high activity against Cryptococcus neoformans with MIC50= 7.8 μg/mL. For anti-Plasmodium falciparum activity the 2-pyrazoline 11b was the most active with EC50= 5.54 μg/mL. Regarding the activity against Trypanosoma cruzi, compound 10a was highly active with EC50= 0.70 μg/mL. Chalcone 8a had good activity against Leishmania panamensis amastigotes with EC50= 0.79 μg/mL.
Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360 Cali, Colombia.
Jonathan
J
Ramírez-Prada
PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, PO Box 1226, Medellín, Colombia.
Sara M
SM
Robledo
PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, PO Box 1226, Medellín, Colombia.
Iván D
ID
Vélez
Grupo de Biotecnología e Infecciones Bacterianas, Departamento de Microbiología, Universidad del Valle, Cali, Colombia; Departamento de Ciencias Biomédicas, Universidad Santiago de Cali, Cali, Colombia.
María Del Pilar
MDP
Crespo
Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360 Cali, Colombia.
Jairo
J
Quiroga
Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360 Cali, Colombia.
Rodrigo
R
Abonia
Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360 Cali, Colombia.
Alba
A
Montoya
Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.
Laura
L
Svetaz
Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.
Susana
S
Zacchino
Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360 Cali, Colombia. Electronic address: braulio.insuasty@correounivalle.edu.co.
Braulio
B
Insuasty
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D011720:Pyrazoles; D011804:Quinolines; C037219:quinoline
2–pyrazolines; Antibacterial activity; Anticancer activity; Antifungal activity; Antileishmanial activity; Antimalarial activity; Antitrypanosomal activity; Chalcones; Quinoline