Synthesis and neuropharmacological activity of some quinoxalinone derivatives

Eight quinoxalinone derivatives were synthesized and investigated for some neuropharmacological effects (analgesia, sedation, convulsion, anxiety, memory and psychosis) in mice and rats. In the CNSdepressant activity, N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide is the mostactive, while the other compounds appear variously dose-dependent. Only three of the compounds showed anxiolytic effect, with N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamideshowing the highest activity at 2.5 mg/kg. At the dose of 30 mg/kg, 6-nitro-1,4-dihydroquinoxaline-2,3-dione showed a better anxiolytic effect in mice than diazepam (dose: 1 mg/kg), while 1,2,3,4-tetrahydroquinoxaline-2,3-dione (dose: 25 mg/kg) showed a comparative effect to diazepam. 6-Chloro-1,4-dihydro-quinoxaline-2,3-dione and N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamideshowed significant anticonvulsant action. None of the compounds showed any analgesic or antidopaminergiceffect. The LD50 (24 h) calculated for the compounds were between 74 and 160 mg/kg i.p

Antimicrobial activity of extracts and a germacranolidetype sesquiterpene lactone from Tithonia diversifolia leaf extract

The in vitro antimicrobial activity of the hexane, ethyl acetate and methanol extracts of the leaf of Tithonia diversifolia, and one sesquiterpene lactone 1 isolated from the ethyl acetate extract wasstudied. Of the fourteen strains of bacteria used, the ethyl acetate extract was the most active, showing inhibitory activity against five Gram +ve and two Gram –ve organisms. This was followed by the hexane extract and then methanol. The ethyl acetate fractions (TDE 2 – TDE 5, TDE 7, TDE 8 and TDE 10) showed varying degrees of inhibitory activity. The sesquiterpene lactone 1 showed activity against all the tested microorganisms, except Staphylococcus aureus and Bacillus cereus (MICs = 15.6 – 62.5mg/ml for most stains). All the extracts, fractions and compound 1 showed activity against the fungusCandida albicans. The results of the present study indicate that the non-polar leaf extract of T.diversifolia could be useful in the treatment of some disease conditions and the sesquiterpene lactone 1 could be a good candidate as a phytotherapeutic agent against some bacterial infection

Antipyretic, analgesic, anti-inflammatory and cytotoxic effects of four derivatives of salicylic acid and anthranilic acid in mice and rats

Four-Substituted derivatives of salicylic and anthranilic acids: 2-hydroxy-5-azidosulfonylbenzoic acid (HASBA, 1), 2-acetyloxy-5- azidosulfonylbenzoic acid (AASBA, 2), 2-acetamido-5- azidosulfonylbenzoic acid (AMASBA, 3) and 2-acetamido-5-sulfonamidobenzoic acid (AMSABA, 4) were synthesized and evaluated for their analgesic, antipyretic, anti-inflammatory and cytotoxic activities. HASBA, AASBA and AMASBA showed higher analgesic activity than aspirin (ASA) at 100 mg/kg dose, while AMSABA showed the least analgesic property. AMASBA exhibited higher antipyretic activity than paracetamol (PCM), while HASBA, AASBA and AMSABA also showed antipyretic effects which were of equal potency to that of PCM. The order of anti-inflammatory effects of the four compounds is: AASBA > AMASBA > HASBA > AMSABA. The effects of the substituents on the biological activities of the synthesized compounds are discussed. Key Words: Salicylic acid derivatives, anthranilic acid, analgesic, anti-inflammatory, antipyretic, cytotoxicity. African Journal of Biotechnology Vol.3(8) 2004: 426-43