1,721,002 research outputs found
Reazione intramolecolare di Friedel-Crafts di indoli con gruppi carbonilici : una semplice sintesi di b-carbolin-1-oni e di diidro-2H-azepino[3,4-b]indol-1-oni
No full textIntramolecular Friedel-Crafts reaction of indoles with carbonyl groups : a simple synthesis of B-carbolin-1-ones and dihydro-2H-azepino[3,4-b]indol-1-ones
No full textNew heterocyclic scaffolds by intramolecular reactions of 4-quinolone-2-carboxamides
No full textThe quinolone moiety is an important structural unit in medicinal chemistry and many compounds with this scaffold have shown a broad range of biological properties including anticancer, antimicrobial, antiviral and antimalarial activity. In pursuance of our research on the development of new antitumor compounds, we became interested in accessing structurally diverse heterocyclic rings containingthe quinolone moiety.We have devised a reliable synthetic route to 4-quinolone-based fused systems starting from 4-quinolone-2-carboxylic acid oxoamides. The acid-catalyzed intramolecular reaction of N-unsubstituted quinolones gives structurally diverse compounds, depending on the length of the chain. Acid treatment of β-oxoamides furnishes 3H-pyrazino[1,2-a]quinoline-4,6-diones, due to the nucleophilic attack of N-1 to the carbonyl group, whereas acid treatment of δ- and ε-oxoamides leads to the formation of tetracyclic compounds by a tandem heteroannulation reaction.
As no examples of such heterocyclic structures have been reported in the literature so far, the sequence represents a versatile approach to new scaffolds andspecifically provides a method for the rapid preparation of differently substituted
derivatives. The results of a preliminary test on compound 2 (m = 1) (IC50 = 10 μM on H460 tumor cell lines) suggest that these classes of compounds could be worth of further investigation
Intramolecular friedel-crafts reaction of indoles with carbonyl groups: a simple synthesis of 3- and 4-substituted β-carbolin-1-ones
Full text linkThe intramolecular Friedel-Crafts reaction of indole-2-carboxylic acid β-oxoamides catalyzed by trifluoroacetic acid or InCl3, is a convenient method for the synthesis of 3-aryl-, 4-aryl-, and 4-alkyl-β-carbolin-1-ones
4-Quinolone fused heterocyclic ring systems by intramolecular reactions of 4-quinolone-2-carboxamides
Full text linkA versatile synthetic route to new 4-quinolone-based polycyclic systems is described. TFA-catalyzed intramolecular reaction of N-unsubstituted quinolone-2-carboxylic acid amides gives structurally diverse compounds, depending on the length of the chain. Acid treatment of β-oxoamides furnishes 3H-pyrazino[1,2-a]quinoline-4,6-diones, due to the nucleophilic attack of N-1 to the carbonyl group, whereas TFA treatment of δ- and ε-oxoamides leads to the formation of tetracyclic compounds by a tandem heteroannulation reaction
Cyclooctadiene anhydride analogues of the natural product zopfiellin as sources of new fungicides
No full textFungicide treatments remain essential to maintain healthy crops and reliable, high-quality yields. However, despite the availability of effective fungicides, new antifungal chemicals are still needed to improve yields and to combat pathogens showing resistance or reduced sensitivity to existing products. Therefore, to develop new generations of antifungal agents, it is crucial to find antifungal compounds with novel chemical scaffolds and new mode of action. For this purpose, Nature has been a very fruitful source of new substances and natural products still exert a strong influence on modern crop protection development, by serving as lead structures for the discovery of active substances, often featuring novel and unique modes of action.
Zopfiellin is a secondary metabolite isolated in 1994 from the ascomycete Zopfiella curvata (Fuckel) Winter. This compound contains a disubstituted cyclooctadiene ring fused with two maleic anhydride moieties and it is endowed with interesting antifungal activity. The mode of action of zopfiellin is still unknown and currently the only method to obtain this compound is the isolation from a fermentation broth of a suitable fungal strain. In this poster we report the preparation of structurally and synthetically simplified zopfiellin analogues containing a cyclooctadiene anhydride nucleus (1), and the evaluation of their in vitro and in vivo antifungal activity. The growth inhibition data on a set of phytopathogen fungi showed that most of the synthesised compounds possessed a broad spectrum of activity. In particular they resulted very effective against the oomycetes Phytophthora infestans and Pythium ultimum, reaching a level of activity well comparable with that of commercial fungicides in use
Design and synthesis of new camptothecin- Pt(II) dual drugs
No full textThe antitumor activity of cis-diaminedichloro-platinum (II) (DDP) was first reported by Rosenberg et al in 1969. The success of cisplatin paved the way for the second- and third-generation platinum(II) drugs, carboplatin and oxaliplatin, and presently platinum-based coordination complexes are among the most widely used antitumour agents in the clinic. Recently, many efforts have been made to overcome severe and sometimes life-threatening toxic side effects of Pt (II) complexes, low cellular uptake and relatively poor pharmacokinetic profiles, often correlated to the activation of drug resistance mechanisms by tumour cells.
In this context we synthesised new Camptothecin-Pt complexes with different Pt-containing linkers ad we modelled their binding to the Topo I covalent complex with DNA
Characterization of new aza-sesquiterpenoids from the fungus Clavicorona Divaricata
No full textMushrooms have proved to be a rich source of secondary metabolites with unusual structures as well as interesting biological activities. Despite their potential for drug development, few bioactive metabolites have been reported from mushrooms as compared with higher plants and microbes. In our screening project on bioactive metabolites of Basidiomycetes we have investigated the metabolites produced by the fungus Clavicorona divaricata in MPG agar cultures and isolated divaricatine A and B together with the nor-sesquiterpenoids tsugicoline L and M. Successively, the fermentation of the fungus in different conditions, gave rise to complex mixtures, from which new aza-sesquiterpenoids were isolated. The poster describes the isolation, structure elucidation and absolute configuration assessment of these novel metabolites The skeleton of these compounds was never found before among the sequiterpenes of protoilludane origin. A possible mechanism of their formation is also suggested.
The new metabolites showed a weak antibacterial activity against Bacillus cereus and Sarcinea lutea (50μg/disc), and inhibited the growth of Lepidum sativum (After 48 h, the inhibition of the root elongation was 85, 91 and 72%, respectively)
Intramolecular N-acyliminium ion versus Friedel-Crafts cyclization onto 3-indoles : synthesis of the novel rings pyrrolizino[2,1-b]indole and homologues
No full textAcid treatment of indole-2-carboxylic acid b- and g-oxoamides causes Friedel–Crafts intramolecular
cyclization to b-carbolinones and dihydro-2H-azepino[3,4-b]indol-1-ones, in contrast to secondary d-,3-,
and z-oxoamides, which cyclize to the novel heterocyclic rings pyrrolizino[2,1-b]indole, indolizino[2,1-b]indole, and 9a,11-diaza-indeno[1,2-a]azulene, via an intermediate N-acyliminium ion. Tertiary amides lead only the Friedel–Crafts ring closure, thus allowing the synthesis of larger fused rings
New captothecin-linked platinum anticancer agents
No full textPresently, platinum-based coordination complexes are among the most widely used antitumor agents in the clinic .The effectiveness of cisplatin lies in its ability to covalently bind DNA, leading to important changes in the helical structure. In spite of the efficacy of platinum-based treatment regimens, long-term cure is difficult to obtain. The major drawbacks include a) severe and sometimes life-threatening toxic side effects; b) activation of drug resistance mechanisms by tumor cells; c) inadequate intratumor concentration of the drug and tumor microenvironmental interactions; d) relatively poor pharmacokinetic profiles and e) increased DNA repair capacity. As part of our program aimed to advance DNA as a drug target, we were interested in devising novel platinum containing dual compounds that interacted in an effective way with DNA and in addition accomplished the requirements of solubility in the body fluids and improved cellular uptake. In this context, a promising approach seemed to be the conjugation of platinum to analogues of the natural antitumor compound camptothecin (CPT).
In this poster we report the design, modeling, synthesis and biological activity evaluation of new hybrid agents formed by CPT derivatives and diaminedichloro-platinum (II) complex. The compounds showed growth inhibitory activity against a panel of human tumor cell lines, including sublines resistant to topotecan and platinum compounds. The derivatives were active in all the tested cell lines, and the most active one was able to overcome cisplatin resistance in the osteosarcoma U2OS/Pt cell line. Platinum-containing camptothecins produced Platinum-DNA adducts and topoisomerase I-mediated DNA damage with cleavage pattern and persistence similar to SN38, the active principle of irinotecan. The results support the interpretation that the diaminedichloro-platinum (II) complex conjugated to a functionalized camptothecin resulted in a new class of effective antitumor compounds
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