amphotericin-b and quinoline

In an attempt for development of new antimicrobial agents, three series of quinoline derivatives bearing pyrazole moiety have been synthesized. The first series was synthesized through the synthesis of 4-(quinolin-2-yloxy)benzaldehyde and 4-(quinolin-2-yloxy)acetophenone and then treatment with ketone or aldehyde derivatives to afford the corresponding chalcones. Cyclization of the latter chalcones with hydrazine derivatives led to the formation of new pyrazoline derivatives. The second series was synthesized via the synthesis of 2-hydrazinylquinoline and then treatment with formylpyrazoles to afford the corresponding hydrazonyl pyrazole derivatives. The third series was synthesized through the treatment of 2-hydrazinylquinoline with ethoxyethylidene, dithioacetal and arylidene derivatives to afford the corresponding pyrazole derivatives. The synthesized compounds were evaluated for their expected antibacterial and antifungal activities; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Pyrazole derivative 13b showed better results when compared with the reference drugs as revealed from their MIC values (0.12-0.98 μg/mL). The pyrazole derivative 13b showed fourfold potency of gentamycin in inhibiting the growth of S. flexneri (MIC 0.12 μg/mL). Also, compound 13b showed fourfold potency of amphotericin B in inhibiting the growth of A. clavatus (MIC 0.49 μg/mL) and C. albicans (MIC 0.12 μg/mL), respectively. The same compound showed twofold potency of gentamycin in inhibiting the growth of P. vulgaris (MIC 0.98 μg/mL), equipotent to the ampicillin and amphotericin B in inhibiting the growth of S. epidermidis (MIC 0.49 μg/mL), A. fumigatus (MIC 0.98 μg/mL), respectively. Thus, these studies suggest that quinoline derivatives bearing pyrazole moiety are interesting scaffolds for the development of novel antibacterial and antifungal agents.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Chemistry Techniques, Synthetic; Drug Synergism; Fungi; Microbial Sensitivity Tests; Pyrazoles; Quinolines; Structure-Activity Relationship

The present study evaluates in vitro the effect of two synthetic compounds of the 7-chloro-4-aryloxyquinoline series, QI (C

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Cell Line; Drug Therapy, Combination; Leishmania donovani; Macrophages; Membrane Potential, Mitochondrial; Mice; Phosphorylcholine; Quinolines

Cutaneous leishmaniasis and Chagas disease are vector-borne parasitic disease causing serious risks to million people living in poverty-stricken areas. Both diseases are a major health problem in Latin America, and currently drugs for the effective treatment of these diseases have important concerns related with efficacy or toxicity than need to be addressed. We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal and trypanocidal activities) of ten quinolone-hydrazone hybrids. The structure of the products was elucidated by spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis which is the most prevalent Leishmania species in Colombia and Trypanosoma cruzi that is the major pathogenic species to humans; in turn, cytotoxicity was evaluated against human U-937 macrophages. Compounds 6b, 6c and 8 showed activity against L. (V) panamensis with EC50 of 6.5 ± 0.8 μg/mL (21.2 μM), 0.8 ± 0.0 μg/mL (2.6 μM) and 3.4 ± 0.6 μg/mL (11.1 μM), respectively, while compounds 6a and 6c had activity against T. cruzi. with EC50 values of 1.4 ± 0.3 μg/mL (4.8 μM) and 6.6 ± 0.3 μg/mL (4.6 μM), respectively. Even compound 6a showed better activity against T. cruzi than the standard drug benznidazole with EC50 = 10.5 ± 1.8 μg/mL (40.3 μM). Analysis of the results obtained against leishmaniasis indicates that antiparasite activity is related to the presence of 2-substituted quinoline (isoquinolinic core) and the hydroxyl group in positions 3 and 4 of the aromatic ring. Although the majority of these compounds were highly cytotoxic, the antiparasite activity was higher than cytotoxicity and therefore, they still have potential to be considered as hit molecules for leishmanicidal and trypanocidal drug development.

Topics: Antiprotozoal Agents; Cell Line; Dose-Response Relationship, Drug; Humans; Hydrazones; Leishmania guyanensis; Macrophages; Molecular Structure; Parasitic Sensitivity Tests; Quinolines; Structure-Activity Relationship; Trypanosoma cruzi

Quinoline amide, azaindole amide and pyridine amides were synthesized and tested for in vitro antifungal activity against fungi. These synthesized amides have potent antifungal activity against Candida albicans and Aspergillus fumigatus. Our results suggest that hetero ring amides may be potent antifungal agents that operate by inhibiting the function of Gwt1 protein in the GPI biosynthetic pathway.

Topics: Amides; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Fungal Proteins; Microbial Sensitivity Tests; Pyridines; Quinolines