Browsing by Author "Quiroga, Jairo"
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Item A facile synthesis of stable β-amino-N-/O-hemiacetals through a catalyst-free three-component Mannich-type reaction(Elsevier Ltd, 2017-03-02) Abonia, Rodrigo; Castillo, Juan C.; Garay, Alexander; Insuasty, Braulio; Quiroga, Jairo; Nogueras, Manuel; Cobo, Justo; D'Vries, Richard F.A practical, straightforward and one-step procedure for the synthesis of novel and stable b-amino-N-/Ohemiacetals (i.e. c-aminoalcohols) is provided. The title compounds were obtained in good to excellent yields through an uncatalyzed three-component reaction by treatment of secondary amines with polyformaldehyde and electron-rich alkenes in acetonitrile as solvent at ambient temperature. The reactions proceeded with the formation of iminium ions, through a Mannich-type reaction, as the key intermediates for the generation of the target products. Single crystal X-ray analysis of derivative 4l confirmed unequivocally the structure and stability of the obtained compounds.Item A facile synthesis of stable β-amino-N-/O-hemiacetals through a catalyst-free three-component Mannich-type reaction(Tetrahedron Letters, 2017) Abonia, Rodrigo; Castillo, Juan C.; Garay, Alexander; Insuasty, Braulio; Quiroga, Jairo; Nogueras, Manuel; Cobo, Justo; D’Vries, Richard F.A practical, straightforward and one-step procedure for the synthesis of novel and stable β-amino-N-/O-hemiacetals (i.e γ-aminoalcohols) is provided. The title compounds were obtained in good to excellent yields through an uncatalyzed three-component reaction by treatment of secondary amines with polyformaldehyde and electron-rich alkenes in acetonitrile as solvent at ambient temperature. The reactions proceeded with the formation of iminium ions, through a Mannich-type reaction, as the key intermediates for the generation of the target products. Single crystal X-ray analysis of derivative 4l confirmed unequivocally the structure and stability of the obtained compounds.Item In silico and in vitro-guided identification of inhibitors of alkylquinolone-dependent quorum sensing in pseudomonas aeruginosa(MDPI AG, 2018-01-28) Soukarieh, Fadi; Oton, Eduard Vico; Dubern, Jean Frédéric; Gomes, Janice; Halliday, Nigel M.; de Pilar Crespo, Maria; Ramírez-Prada, Jonathan; Insuasty O, Braulio; Abonía, Rodrigo; Quiroga, Jairo; Heeb, Stephan; Williams, Paul M.; Stocks, Michael John; Cámara, Miguel ÁngelPseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P. aeruginosa mCTX::PpqsA-lux chromosomal promoter fusion, to identify a series of new PqsR antagonists. The hit compounds inhibited pyocyanin and alkylquinolone signal molecule production in P. aeruginosa PAO1-L and PA14 strains. The inhibitor Ia, which showed the highest activity in PA14, reduced biofilmformation in PAO1-L and PA14, increasing their sensitivity to tobramycin. Furthermore, the hepatic and plasma stabilities for these compounds were determined in both rat and human in vitro microsomal assays, to gain a further understanding of their therapeutic potential. This work has uncovered a new class of P. aeruginosa PqsR antagonists with potential for hit to lead optimisation in the search for quorum sensing inhibitors for future anti-infective drug discovery programs. © 2018 by the authors.Item Methoxyquinolone–Benzothiazole Hybrids as New Aggregation-Induced Emission Luminogens and Efficient Fluorescent Chemosensors for Cyanide Ions(MDPI, 2024) Mutis Ayala, Mario; Trilleras, Jorge; D’Vries, Richard; Macías, Mario A.; Insuasty, Alberto; Abonia, Rodrigo; Quiroga, Jairo; Illicachi, Luis A.; Márquez, Edgar; Insuasty, DanielThis work describes the synthesis and characterization of new quinolone–benzothiazole hybrids, the study of their aggregation-induced emission (AIE) properties, and the use of these systems as efficient fluorescent probes for cyanide ions. These conjugated derivatives are linked through a double bond favoring electronic communication, and together with their planar geometry, can strongly aggregate under solvophobic environments, leading to aggregation and exhibiting significant AIE behavior. The double bond between electroactive units is prone to nucleophilic addition reactions by cyanide ions, selectively, conducive to turning off the fluorescence properties, making this hybrid system an efficient probe for cyanide ions. These studies were theoretically explained using DFT and TD-DFT calculations.Item Synthesis of novel quinoline–based 4,5–dihydro–1H–pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents(Elsevier Masson SAS, 2017-03-16) Ramírez Prada, Jonathan; Robledo, Sara M.; Velez, Ivan D.; Crespo, María del Pilar; Quiroga, Jairo; Abonia, Rodrigo; Montoya, Alba; Svetaz, Laura; Zacchino, Susana; Insuasty, BraulioA new series of Nesubstituted 2epyrazolines 9aef, 10aef, 11aef, 12aef and 13aef were obtained from the cyclocondensation reaction of [(7echloroquinoline4eyl)amino]chalcones 8aef 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 GI50 values ranging from 0.28 to 11.7 mM (0.13e6.05 mg/ mL) and LC50 values ranging from 2.6 to > 100 mM (1.2 to > 51.7 mg/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 mg/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 ¼ 7.8 mg/mL. For antiePlasmodium falciparum activity the 2epyrazoline 11b was the most active with EC50 ¼ 5.54 mg/mL. Regarding the activity against Trypanosoma cruzi, compound 10a was highly active with EC50 ¼ 0.70 mg/mL. Chalcone 8a had good activity against Leishmania panamensis amastigotes with EC50 ¼ 0.79 mg/mL.Item Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents(MDPI, 2024) Moreno, Leydi M.; Quiroga, Jairo; Abonia, Rodrigo; Crespo, María del P.; Aranaga, Carlos; Martínez Martínez, Luis; Sortino, Maximiliano; Barreto, Mauricio; Burbano, María E.; Insuasty, BraulioThis study presents the synthesis of four series of novel hybrid chalcones (20,21)a–g and (23,24)a–g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28–33)a–g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d–g, 24a–g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e–g, 33a,b,e–g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 μM and LC50 values in the range of 4.09 μM to >100 μM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25–62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 μg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.