Synthesis and antibacterial evaluation of [S,Z]-4-methyl-2-[4-oxo-5- [[5-substituted phenylfuran-2-yl] methylene]-2-thioxothiazolidin-3-yl] pentanoic acids

The microbial resistance has become a global hazard with the irrational use of antibiotics. Infection of drug-resistant bacteria seriously threatens human health. Currently, there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of [S,Z]-4-methyl-2-[4-oxo-5-[[5-substitutedphenylfuran-2- yl] methylene]-2-thioxothiazolidin-3-yl]pentanoic acids via a Knoevenagel condensation were synthesized and evaluated for their antibacterial activity in-vitro. The synthesized compounds were characterized by IR, [1]H NMR and MS. The antibacterial test in-vitro showed that all of the synthesized compounds had good antibacterial activity against several Gram-positive bacteria [including multidrug-resistant clinical isolates] with minimum inhibitory concentration [MIC] values in the range of 2-4 micro g/mL. Especially compounds 4c, 4d, 4e and 4f were the most potent, with MIC values of 2 micro g/mL against four multidrug-resistant Gram-positive bacterial strains

Synthesis and anticonvulsant evaluation of some new 6-[substituted-phenyl] thiazolo[3,2-b][l,2,4]triazole derivatives in mice

Epilepsy is the most frequent nearological affiction and afflicts 1% about of the worlds population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-[substituted-phenyT] thiazolo[3,2-b][1.2.4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock [MES] and subcutaneous pentylenetetrazole [PTZ] screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-[4-fluorophenyl] thiazolo[3,2-b][l,2,4]triazole [3c] showed selective protection against the MES seizures with an ED[50] value of 49.1 mg/Kg and a TD[50] value of 94.1 mg/Kg, which provided compound 3c a protective index [PI = TD[50]/ED[50] of 1.9 in the MES test. 6-[4-Propoxyphenyl]thiazolo[3,2-b][l,2,4]triazole [5b] was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED[50] of 63.4 mg/Kg and a TD[50] of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine

Synthesis of novel 7-substituted-5-phenyl-[l92,4]triazolo[l,5-a] pyrimidines with anticonvulsant activity

Considerable interest has been focused on the triazole structure, which has been known to possess a broad spectrum of biological activities such as antitumor, anti-inflammatory, antimicrobial, antiviral, and anticonvulsant activities. Before this, several heterocyclic compounds containing triazole were synthesized that had shown considerable anticonvulsant activity. As part of our continuous research in this area, we have synthesized several new 7-substituted-5-phenyl-[1, 2, 4] triazolo[l, 5-#] pyrimidines [compounds 3a-3i, 5a-5micro] through incorporating triazole moiety into the pyrimidine ring, which are expected to have the synergistic effect in dealing with the epilepsy. Their anticonvulsant activities were measured through the Maximal electroshock [MES] test. Carbamazepine and valproate were considered as positive control drugs with anticonvulsant effects [ED[50] = 11.8 and 272 mg/Kg]. Amongst the compounds tested, compound 3f, 7-[heptyloxy]-5-phenyl-[l, 2, 4] triazolo[l, 5-a] pyrimidine, showed potent anticonvulsant activity with ED[50] 84.9 mg/Kg, which was weaker than carbamazepine, but better than valproate