Quinoline based furanones and their nitrogen analogues: Docking, synthesis and biological evaluation.
A small library of twenty-four quinoline based butenolides also known as furanones and their nitrogen analogues was prepared by using two different aroylpropionic acids, viz. 3-(2-naphthoyl)propionic acid (3) and 3-(biphenyl-4-yl)propionic acid (4), as starting materials. The 3-aroylpropionic acids were reacted with different 6-substituted-2-chloroquinolin-3-carbaldehydes (2a-d) to obtain the corresponding furan-2(3H)-ones (5a-h). The purified and characterized furanones were then converted into their corresponding 2(3H)-pyrrolones (6a-h) andN-benzyl-pyrrol-2(3H)-ones (7a-h). The antimicrobial activities of the title compounds were evaluated against two strains of each Gram +ve (Staphylococcus aureusandBacillus subtilis), Gram -ve bacteria (Escherichia coliandPseudomonas aeruginosa) and against fungal strains ofAspergillus nigerandAspergillus flavus.In vivoanti-inflammatory potential of the title compounds was investigated by standard method. Majority of the compounds showed significant antibacterial activity against both the Gram +ve strains. Eight most potent anti-inflammatory compounds (5b, 5d, 5h, 6b, 7b, 7d, 7f, 7h)which exhibited >53% inhibition in edema, were also screened for theirin vivoanalgesic activity. All the tested compounds were found to have significant reduction in ulcerogenic action but only three compounds (5d, 5hand7h) showed comparable analgesic activity to standard drug, diclofenac. The results were also validated usingin silicoapproach and maximum mol doc score was obtained for compounds7a-h. On comparing thein vivoandin silico anti-inflammatoryresults of synthesized compounds,N-benzyl pyrrolones (7a-h) emerged as the potent anti-inflammatory agents. It was also observed that compounds that possess electron withdrawing group such as -Cl or NO2are more biologically active.
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India.
Sukhbir Lal
SL
Khokra
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India.
Jyoti
Department of Microbiology, Kurukshetra University, Kurukshetra, Haryana, India.
Chetan
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India.
Pawan
P
Kaushik
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
M M
MM
Alam
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
M S
MS
Zaman
Health Information Technology Department, Jeddah Community College, King Abdulaziz University, Jeddah, Saudi Arabia.
Aftab
A
Ahmad
Department of Pharmacy, Oman Medical College, Muscat, Oman.
Shah Alam
SA
Khan
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Asif
A
Husain
Analgesic; Anti-inflammatory; Antimicrobial; Butenolide; In silico; Pyrrolone