Synthesis of quinoline attached-furan-2(3H)-ones having anti-inflammatory and antibacterial properties with reduced gastro-intestinal toxicity and lipid peroxidation

Abstract

A series of 3-[2-chloroquinolin-3-yl)methylene]-5-aryl-furan-2(3H)-ones {3(a-p)} were synthesized. The required 3-(substitutedbenzoyl) propionic acids {2(a-d)} were prepared under Friedal Craft acylation reaction conditions. The substituted 2-chloroquinoline-3-carbaldehydes {1(a-d)} were synthesized by reaction of substitutedphenylethanone-oxime with phosphorus oxychloride in presence of dimethyl formamide using the Vilsmeir Haack reaction method. These compounds were screened for their anti-inflammatory and antibacterial activities along with their ulcerogenic and lipid peroxidation potentials. The compounds that showed significant anti-inflammatory activity were further screened for their analgesic activity. The compounds were less toxic in terms of ulcerogenicity as compared to a standard, which was also supported by lipid peroxidation studies. The antibacterial activities were performed against Staphylococcus aureus and Escherichia coli. Compounds 3f, 3n and 3o showed significant activity against both S. aureus and E. coli having an MIC value of 6.25μg mL-1

Reactions of 5-(4-methoxy-3-methylphenyl)-2(3H)-furanone with some electrophilic and nucleophilic reagents

“…Elemental analyses were performed on a flash EA-1112 instrument. 1 H NMR spectra were measured on Bruker (300 MHz) instrument and TMS was used as internal standard. IR spectra were recorded on a Perking Elmer 1430 ratio recording infrared spectrophotometer with CDS data station using KBr Wafer technique.…”

“…Compounds incorporating such heterocycles in their structure have been found to display broad spectrum of biological activities including anti-inflammatory [1][2][3], cardiotonic activity [4], analgesic [5], anticancer [6], anti-convulsant [7], anti-microbial [8] and antiviral activeties [9].…”

Utility of novel 2-furanones in synthesis of other heterocyclic compounds having anti-inflammatory activity with dual COX2/LOX inhibition

“…These heterocycles acquired an obvious medicinal interest as antimicrobial [22][23][24] , antiviral [25][26][27] , antimycobacterial 28,29 , and anti-cancer agents [30][31][32] . Literature is enriched with different 2-furanones subjected to ring opening to form 2-pyrrolone, pyridazinone, and oxadiazole derivatives, all have high activity as anti-inflammatory 24,[33][34][35][36][37][38][39][40][41] . As shown in Figure 1, 2-furanone derivatives Ia-c were reported to exhibit comparable anti-inflammatory activity to that of diclofenac 33,35,36 , while 2-pyrrolone derivatives II, IIIa-b, and IV were reported to have comparable anti-inflammatory activity to that of indomethacin, ibuprofen, and diclofenac, respectively 24,[34][35][36] .…”

Aminoquinoline Schiff Bases as Non-Acidic, Non-Steroidal, Anti-Inflammatory Agents

“…The traditional non‐steroidal anti‐inflammatory drugs (NSAIDs) bearing acidic groups (pKa=3.5‐5.5) such as diclofenac, indomethacin, aspirin, ibuprofen etc . caused gastrointestinal tract (GIT) irritation, and ultimately ulceration ,…”