Giuseppe Daidone

Synthesis and pharmacological study of ethyl 1-methyl-5-(substituted 3,4-dihydro-4-oxoquinazolin-3-yl)-1H-pyrazole-4-acetates.

Several new ethyl 1-methyl-5-(substituted 3,4-dihydro-4-oxoquinazolin-3-yl)-1H-pyrazole-4-acetates 2, substituted at 2 and, alternatively at, 6, 7 or 8 positions of the quinazolinone nucleus, were synthesised. The compounds were screened for their analgesic and antiinflammatory activities, acute toxicity and ulcerogenic effect. Substitution in the benzene moiety of the quinazolinone ring did not show any advantage for the analgesic activity, whereas it improved in some cases the antiinflammatory activity. Some compounds showed appreciable antiinflammatory activity and, at the same time, very low ulcerogenic index.

Synthesis and pharmacological activities of novel 3-(isoxazol-3-yl)-quinazolin-4(3H)-one derivatives.

Several new 3‐(isoxazol‐3‐yl)‐quinazolin‐4(3H)‐one derivatives were synthesized and tested for their analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effect. A few compounds were as active as phenylbutazone in the writhing and acetic acid peritonitis tests. They had a very low ulcerogenic effect.

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 active against tumor cell lines, with inhibitory activity (IC 50 ) in the range 2.4–20 μM and bacteria. The highest microbial susceptibility was shown by gram-positive bacteria, with minimum inhibitory concentrations in the range 0.8–12.5 μM.

Synthesis and pharmacological study of ethyl 1-methyl-5-[2-substituted-4-oxo-3(4H)-quinazolinyl]-1H-pyrazole-4-acetates

Abstract A number of new ethyl 1-methyl-5-[4-oxo-3(4 H )-quinazolinyl]-1 H -pyrazole-4-acetates substituted at the 2 position of the quinazolinone ring were prepared. The compounds were tested for analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effect. The 2-methyl, 2-ethyl and 2-phenyl derivatives proved to be more active than acetylsalicylic acid and phenylbutazone in the phenylbenzoquinone writhing test. The 2-methyl derivative was also as active as acetylsalicylic acid in the carrageenin paw oedema test. All the compounds showed very reduced ulcerogenic effects and systemic toxicity.

Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle.

In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules.

Synthesis and antiproliferative activity of novel 3-(indazol-3-yl)-quinazolin-4(3H)-one and 3-(indazol-3-yl)-benzotriazin-4(3H)-one derivatives.

Several new 3‐(indazol‐3‐yl)‐quinazolin‐4(3H)‐one and 3‐(indazol‐3‐yl)‐benzotriazin‐4(3H)‐one derivatives 5 and 6 were synthesized and tested for their in vitro antiproliferative activity against Raji, K562, and K562‐R cell lines. The pharmacological screening showed that some 2, 6, or 7‐substituted quinazolinones 5 posses a significant antiproliferative activity, with a percentage growth inhibition ranging from 44.8% to 100% at 50 μM, which was higher than that showed by the unsubstituted derivative 5a previously synthesized. For the most active compounds 5d, 5f, and 5g the IC50 were recorded.

Sortase A Inhibitors: Recent Advances and Future Perspectives

Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be comprehensively evaluated in in vivo models of infection, in order to select compounds eligible for the treatment of bacterial infections in humans.

Synthesis and antifungal activity of new N-isoxazolyl-2-iodobenzamides

N-Isoxazolyl-2-iodobenzamides 3 and 9, with a benodanil-like structure, were synthesized by refluxing in acetic acid the corresponding benzotriazinones 2 and 8 with potassium iodide for 1 h with the aim to ascertain if they were active as fungicides against Phytophthora citricola Saw., Botrytis cinerea Pers., Rhizoctonia sp. and Alternaria sp. Among the tested iodo derivatives, compounds 3b and 9a possess interesting activities against the aforesaid fungal strains in several cases similar to that of benodanil I taken as reference drug.

Recent discoveries of anticancer flavonoids

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 the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported.

Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[(2E)-3-phenylprop-2-enoyl]amino}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 most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.