Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones

In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 microg ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC(50) value of 5.8 v…

Antimicrobial and antineoplastic activities of new 4-diazopyrazole derivatives

Abstract Several new 4-diazopyrazole derivatives were prepared by the reaction of 3-methyl-5(substituted-benzamido)pyrazoles with an excess of nitrous acid in acetic acid solution. The compounds were tested for antiretroviral activity in HIV-1 infected MT-4 cells and antiproliferative effects against a panel of human leukemia, lymphoma and solid tumor cell lines. They were also tested for activity against representative gram-negative ( Shigella, Salmonella ) and gram-positive ( S. aureus, D group Streptococcus ) bacteria as well as fungi ( C. albicans, C. paratropicalis, C. neoformans and A. fumigatus ). Compounds were devoid of anti HIV-1 and antimicotic activities, whereas they were activ…

Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[2E]-3-phenylprop-2-enoylamino}benzamides

Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a–s and 17t–v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl)acrylic acid chlorides 11c–k and 11t–v with the appropriate anthranilamide derivatives 10a–c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the mo…

Phenylamides of 1-Phenyl (or Methyl)-5-benzamidopyrazole-4-carboxylic Acid as Vratizolin Analogs with Analgesic and Antiinflammatory Activities

A number of phenylamides of 5-benzamidopyrazole-4-carboxylic acid were prepared in 50-80 % yields from 1-phenyl (or methyl) 6-phenylpyrazolo[3,4-d]1,3-oxazin-4(1H)-ones and aniline derivatives. All the compounds were tested for their analgesic and antiinflammatory activities, as well as for their ulcerogenic potential and acute toxicity. Some derivatives, when compared to phenylbutazone, proved more active in the tests for analgesie and antiexudative activities, but less active in the carrageenin paw oedema test. The compounds proved to posses marginal or no ulcerogenic effect, as well as low systemic toxicity.

Recent discoveries of anticancer flavonoids.

Abstract In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated t…

4-(3H)-quinazolinones N-3 substituted with a five membered heterocycle: A promising scaffold towards bioactive molecules

Abstract The quinazolinone nucleus represents, among the class of fused heterocycles, a very important scaffold to obtain molecules with biological activities. A review of literature revealed how such kind of fused heterocycles, coming from natural or synthetic source, are associated with a wide range of biological activities. This review is mainly directed towards the 4-(3H)-quinazolinones N-3 substituted with a five membered heterocycle in which all the possible combinations of nitrogen, sulfur and oxygen atoms are present.

Synthesis and pharmacological evaluation of 1-methyl-5- [substituted-4(3H)-oxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acid derivatives

Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test. All the compounds inhibited the 3 alpha-HSD, but no correlation was observed with …

4-Diazopyrazole Derivatives as Potential New Antibiofilm Agents

<i>Background:</i> The recognition that chronic infections and infections associated with medical devices are biofilm related has been the impulse for investigating the antibiofilm properties of some diazopyrazoles biologically active as antimicrobials. <i>Methods:</i> The susceptibility of staphylococcal biofilms was determined at concentrations ranging from 25 to 1.5 µg/ml using crystal violet and methylthiazotetrazolium (MTT) staining. In the case of <i>Candida albicans,</i> we first assessed the anti-germ tube formation effect of 4-NO<sub>2</sub> (compound 1c) and then we evaluated its antibiofilm activity at concentrations ranging from 10…

Facile synthesis of 5-benzamido-4-diazopyrazole derivatives, a class of biologically active agents and key intermediates

Abstract By reacting l-R1-3-R2-5-(R3-substituted)benzamidopyrazoles with a great ex-cess of nitrous acid in acetic acid media, the related 4-diazoderivatives in 65–80% yields were obtained.

2-Cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido)benzamides: synthesis, antiproliferative activity, and mechanism of action

Abstract Several new benzamides 4a–q were synthesized by stirring in pyridine the acid chlorides 3a–q with the appropriate anthranilamide derivatives 2a–g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemia cells, MCF-7 breast cancer cells, HTC-116 and HT26 colon cancer cells and NCI H460 non-small cell lung cancer cells).

Synthesis, crystallographic studies and biological evaluation of some 2-substituted 3-indazolyl-4(3H)-quinazolinones and 3-indazolyl-4(3H)-benzotriazinones

Pyrazolo[3,4‐d]pyrimidine Derivatives as COX‐2 Selective Inhibitors: Synthesis and Molecular Modelling Studies

The pyrazolo[3,4-d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti-inflammatory activity of 5-benzamido-pyrazolo[3,4-d]pyrimidin-4-one derivatives and considering the easy synthesis of this class of compounds, a set of new 5-benzamido-1H-pyrazolo[3,4-d]pyrimidin-4-ones has been prepared in 42-80% yields by reacting 5-aminopyrazole-4(N-benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a-d, and 11a, b revealed a superior inhibitory profile against COX-2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological results.