ABSTRACT
The novel hybrids with 1,2,3-triazole and polyhydroquinoline scaffolds were successfully synthesized by multicomponent reaction of propargyloxybenzaldehyde, 1,3-cyclohexadione, ethylacetoacetate and ammonium acetate followed through click reaction in the presence of deep eutectic solvent ChCl/ZnCl2 as an efficient catalyst. Their anti-leishmanial activity was evaluated against amastigote and promastigote forms of L. tropica, L. major, and two different species of L. infantum. Furthermore, to determine the cytotoxicity of the hybrids, they were evaluated against the murine macrophage cell line J774.A1. Based on the results, three hybrids showed the highest antileishmanial activity. However, they revealed low cytotoxicity. Hybrid 6j was the most potent compound against both the forms of all leishmanial types, with IC50 = 13.5 and 11.9 µg/mL for L. major, 37.5 and 25 µg/mL for L. tropica, 17.5 and 20 µg/mL for L. infantum (MCAN/IR//96/LON49) and 35.5 and 30 µg/mL for L. infantum (MCAN/ES/98/LIM-877), respectively. Finally, molecular docking and molecular dynamics simulations were also performed to identify possible mechanism antileishmanial activity.Communicated by Ramaswamy H. Sarma.
ABSTRACT
One palladium-catalyzed sequential coupling reactions were successfully used as a new protocol for the synthesis of unsymmetrical 2,3-diethynyl quinoxalines and 4-ethynyl-substituted pyrrolo[1,2-a]quinoxalines. The one-pot two coupling reactions of 2,3-dichloroquinoxaline, with two different terminal alkynes, under controlled conditions produced selectively unsymmetrical 2,3-diethynyl quinoxalines with high yields. When one of the two terminal alkynes was 3-propyne-1-ol, in the presence of secondary amines, cyclization occurred and 4-ethynyl-substituted pyrrolo[1,2-a]quinoxalines were successfully formed. All synthesized compounds were tested against the two bacterial strains including Micrococcus luteus and Pseudomonas aeruginosa.
Subject(s)
Anti-Bacterial Agents , Pyrroles , Quinoxalines , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Catalysis , Micrococcus luteus/drug effects , Micrococcus luteus/growth & development , Palladium/chemistry , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Pyrroles/chemical synthesis , Pyrroles/chemistry , Pyrroles/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/chemistry , Quinoxalines/pharmacologyABSTRACT
The salophen copper(II) complex was successfully used for the efficient synthesis of new 1,2,3-triazoles based on the naphthalene-1,4-dione scaffold. The reaction of 2-chloro-3-(prop-2-yn-1-yloxy)naphthalene-1,4-dione or 2,3-bis(prop-2-yn-1-yloxy)naphthalene-1,4-dione with aromatic azides in the presence of a low copper catalyst (loading 1â mol-%) afforded 2-chloro-3-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]naphthalene-1,4-dione or 2,3-bis[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]naphthalene-1,4-dione, respectively. The advantages of these reactions are short reaction times, high-to-excellent reaction yields, operational simplicity, and mild experimental conditions. The new 1,2,3-triazoles obtained were screened for their inâ vitro antibacterial activities and were subjected to molecular docking studies.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Click Chemistry , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Copper/chemistry , Naphthalenes/chemistry , Salicylates/chemistry , Triazoles/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Microbial Sensitivity Tests , Molecular Docking Simulation , ThermodynamicsABSTRACT
Synthesis of 2,3-disubstituted 1-alkylpyrrolo[2,3-b]quinoxalines was accomplished through the reaction of 3-chloroquinoxalin-2-amines with internal alkynes in the presence of Pd(OAc)[Formula: see text], NaOAc, and KOtBu in DMSO. This method afforded desired pyrrolo[2,3-b]quinoxalines in 65-92% reaction yields. The minimum inhibition concentration and minimum bactericidal concentration determinations against Micrococcus luteus and Pseudomonas aeruginosa revealed that some of the synthesized compounds showed the same values compared to tetracycline. These compounds could be used in the future research for the development of new antibiotics.
Subject(s)
Alkynes/chemistry , Anti-Bacterial Agents/chemical synthesis , Palladium/chemistry , Quinoxalines/chemical synthesis , Anti-Bacterial Agents/pharmacology , Catalysis , Microbial Sensitivity Tests , Micrococcus luteus/drug effects , Micrococcus luteus/growth & development , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Quinoxalines/pharmacology , Structure-Activity RelationshipABSTRACT
The reactions of several 2-chloroquinoline-3-carboxylate esters with propargyl alcohol and a secondary amine in the presence of palladium catalyst leads to the formation of new alkyl 1-amino substituted pyrrolo[1,2-a]quinoline-4-carboxylate derivatives. This one-pot process, carried out in the absence of any copper salt, provides an efficient method for the synthesis of functionalized pyrrolo[1,2-a]quinolines in good-to-high yields.