Synthesis of Amide Derivatives as Preclinical Drug Candidates for Visceral Leishmaniasis
Session Number
Project ID: CHEM 12
Advisor(s)
Dr. John Thurmond, Illinois Mathematics and Science Academy
Discipline
Chemistry
Start Date
17-4-2024 8:55 AM
End Date
17-4-2024 9:10 AM
Abstract
Visceral Leishmaniasis (VL) is a lethal protozoan disease caused by numerous species of the Leishmania genus, manifesting symptoms like fever, spleen and liver enlargement, progressive weight loss, and anemia. In this experiment, three potential VL drug amide derivatives were synthesized using multiple coupling agents and methods. The objective of each trial was to isolate a compound effective in treating Leishmaniasis caused by the species Leishmania (L.) dovani and L. infantum, which will be tested by the Drugs for Neglecte Diseases Initiative (DNDi) organization. The first two trials utilized DMAP and EDCI coupling agents and physical homogenization, while the third trial necessitated pyridine and a heated homogenization process. The first two trials reacted 3-fluorobenzoic acid with 2-amino-5-chlorobenzoxazole, and 3(trifluoromethyl)phenylacetic acid with 2-amino-5-chlorobenzoxazole, respectively—the third trial employed pyridine-2-carbonyl chloride HCL and 2- amino-5-chlorobenzoxazole. After synthesis, products were isolated through a separatory funnel and dried over sodium sulfate. Purity testing using thin-layer chromatography with a 1:1 hexane and ethyl acetate solvent ratio was conducted, followed by silica gel column chromatography with a 3:1 hexane to ethyl acetate ratio for product determination and isolation. Infrared spectroscopy confirmed the presence of each compound. The synthesized compounds will be delivered to DND's laboratory for efficacy, based on surface area polarity, cytotoxicity, and Leishmania activity.
Synthesis of Amide Derivatives as Preclinical Drug Candidates for Visceral Leishmaniasis
Visceral Leishmaniasis (VL) is a lethal protozoan disease caused by numerous species of the Leishmania genus, manifesting symptoms like fever, spleen and liver enlargement, progressive weight loss, and anemia. In this experiment, three potential VL drug amide derivatives were synthesized using multiple coupling agents and methods. The objective of each trial was to isolate a compound effective in treating Leishmaniasis caused by the species Leishmania (L.) dovani and L. infantum, which will be tested by the Drugs for Neglecte Diseases Initiative (DNDi) organization. The first two trials utilized DMAP and EDCI coupling agents and physical homogenization, while the third trial necessitated pyridine and a heated homogenization process. The first two trials reacted 3-fluorobenzoic acid with 2-amino-5-chlorobenzoxazole, and 3(trifluoromethyl)phenylacetic acid with 2-amino-5-chlorobenzoxazole, respectively—the third trial employed pyridine-2-carbonyl chloride HCL and 2- amino-5-chlorobenzoxazole. After synthesis, products were isolated through a separatory funnel and dried over sodium sulfate. Purity testing using thin-layer chromatography with a 1:1 hexane and ethyl acetate solvent ratio was conducted, followed by silica gel column chromatography with a 3:1 hexane to ethyl acetate ratio for product determination and isolation. Infrared spectroscopy confirmed the presence of each compound. The synthesized compounds will be delivered to DND's laboratory for efficacy, based on surface area polarity, cytotoxicity, and Leishmania activity.