Synthesis, Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido, Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives.

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a-e), pyrido[2',3':4,5]thiazolo[2,3-b]quinazolines {5(a-e), 6(a-e), and 7(a-e)}, pyrano[2',3':4,5]thiazolo[2,3-b]quinazolines 8(a-e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a-e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 µg/mL while the others exhibited better antibacterial activity at 100 µg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, 1H-NMR, and 13C-NMR.

In vitro biological activity of aromadendrin-4'-methyl ether isolated from root extract of Ventilago madraspatana Gaertn with relevance to anticandidal activity.

In this study, antimicrobial and antioxidant activities of the hexane extract of the root of Ventilago madraspatana were evaluated. Based on the significant bioactivity of crude hexane extract, an active compound was purified from the root extract. The active compound was further purified and identified as aromodendrin-4'-methyl ether by the (1)H NMR spectrum. The isolated compound significantly inhibited Staphylococcus epidermidis with the lowest MIC and MBC at 78 µg/mL (P < 0.05). The compound also exhibited significant anticandidal activity with MIC and MBC values of 312 and 625 µg/mL, respectively. The radical scavenging activity of aromodendrin-4'-methyl ether was evident by its lower IC50 values of 60 µg/mL for DPPH scavenging and 3.2 µg/mL for ABTS scavenging. The compound also exhibited ferrous ion chelation and H2O2 scavenging activities. The study is an attempt to increase the industrial utility of V. madrasapatana.

Synthesis and evaluation of antioxidant and antibacterial activities of new substituted bis(1,3,4-oxadiazoles), 3,5-bis(substituted) pyrazoles and isoxazoles.

Two series of five membered heterocyclic bis(1,3,4-oxadiazole) derivatives 2(a-h) and 3,5-bis(substituted)pyrazoles, isoxazoles 3(a,b,d-i), 4(a-c) were synthesized via oxidative cyclization of some diaroylhydrazones using chloramine-T and cyclocondensation reaction with hydrazine hydrate and hydroxylamine hydrochloride, respectively. The newly synthesized compounds were screened for antioxidant and anti-microbial activities. Compounds 2(b), 3(b), and 4(a) showed higher antioxidant activity at 10 µg/ml while compounds 2(a), 3(a), 3(f), and 4(a) exhibited better anti-microbial activity at 100µg/ml compared with standard vitamin C and ciprofloxacin, respectively. Structures of newly synthesized compounds were confirmed by elemental analysis and spectral IR, (1)H NMR, and (13)C NMR data.

Antiangiogenic and antiproliferative effects of substituted-1,3,4-oxadiazole derivatives is mediated by down regulation of VEGF and inhibition of translocation of HIF-1alpha in Ehrlich ascites tumor cells.

PURPOSE: 1,3,4-Oxadiazoles are an important class of heterocyclic compounds, which play a pivotal role in various pharmaceutical applications. Here, we investigated the antiangiogenic and antiproliferative effects of the derivatives and explored its mechanism of action on EAT cells. METHODS: The cytotoxic effect of the derivatives on EAT and HEK293 cells was assessed by MTT assay. Effect of the derivatives on ALP activity and proliferation was measured. Swiss albino mice transplanted with EAT cells were used as a model system to study the effect of the derivatives in vivo. Inhibition of angiogenesis in mice peritoneum, CAM and Cornea of the rat were studied. Finally, the effects on VEGF gene expression, HIF-1alpha translocation and cell cycle arrest were determined. RESULTS: The IC50 range for growth inhibition of EAT cells was found to be 140-175 microM. In contrast normal HEK293 cells were resistant to the derivatives at this range. Treatment with derivatives in vivo was demonstrated by the down regulation of VEGF in EAT cells and inhibition of blood vessels formation in mice peritoneum, CAM and cornea of rat, indicating the potent angioinhibitory effect of the derivatives. VEGF promoter-luciferase reporter gene expression analysis showed suppression of VEGF gene expression in vitro. The derivatives proved to be potent antiproliferative agents as shown by FACS analysis and decreased ALP activity. Furthermore, expression of HIF-1alpha was also down regulated by derivatives by repressing its nuclear translocation. CONCLUSIONS: Oxadiazole derivatives are strong bioactive compounds with antiangiogenic and antiproliferative potential both in vitro and in vivo. We postulate that diminished HIF-1alpha nuclear presence in oxadiazole treated EAT cells could be responsible for decreased VEGF expression and antiangiogenic effects.