Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4’-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer 15 stands out due to its cytotoxic potencies at submicromolar concentrations and high selectivity index (mean IC50 = 0.37 μM; SI = 6.97) compared to those of etoposide (mean IC50 = 3.67; SI = 0.32) and taxol (mean IC50 = 0.35; SI = 0.91) employed as reference anticancer drugs

Prenylated Flavonoids with Potential Antimicrobial Activity: Synthesis, Biological Activity, and In Silico Study

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7–13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 40 are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.Fil: Osorio, Mauricio. Universidad Técnica Federico Santa María, Departamento de Química. Chile.Fil: Caravajal, Marcela.Universidad Técnica Federico Santa María. Centro de Biotecnología CB-DAL. Chile.Fil: Vergara, Alejandra. Universidad Técnica Federico Santa María. Centro de Biotecnología CB-DAL. Chile.Fil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Farmacognosia. Argentina.Fil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Farmacognosia. Argentina.Fil: Zaccchiano, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Farmacognosia. Argentina.Fil: Mascayano, Carolina. Universidad de Santiago de Chile. Facultad de Química y Biología. Departamento de Ciencias del Ambiente. Chile.Fil: Montoya, Margarita. Universidad de Santiago de Chile. Facultad de Química y Biología. Departamento de Biología. Chile.Fil: Mejías, Sophia. Universidad de Santiago de Chile. Facultad de Química y Biología. Departamento de Biología. Chile.Fil: Cortez-San Martín, Marcelo. Universidad de Santiago de Chile. Facultad de Química y Biología. Departamento de Biología. Chile.Fil: Vásquez-Martínez, Yesseny. Universidad de Santiago de Chile. Facultad de Ciencias Médicas. Escuela de Medicina. Programa Centro de Investigaciones Biomédicas Aplicadas. Chil

Prenylated flavonoids with potential antimicrobial activity: synthesis, biological activity, and in silico study

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7–13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 4′ are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.Fil: Osorio, Mauricio. Universidad Técnica Federico Santa María; ChileFil: Carvajal, Marcela. Universidad Técnica Federico Santa María; ChileFil: Vergara, Alejandra. Universidad Técnica Federico Santa María; ChileFil: Butassi, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Mascayano, Carolina. Universidad de Santiago de Chile; ChileFil: Montoya, Margarita. Universidad de Santiago de Chile; ChileFil: Mejías, Sophia. Universidad de Santiago de Chile; ChileFil: Cortés San Martín, Marcelo. Universidad de Santiago de Chile; ChileFil: Vásquez Martínez, Yesseny. Universidad de Santiago de Chile; Chil