136 research outputs found
In vitro antitumorsko i antivirusno djelovanje novih benzotiazola i 1,3,4-oksadiazol-2-tion derivata
A series of new benzothiazole derivatives 6a-h have been synthesized, in five steps, from substituted phenols via the 1,3,4-oxadiazole-2-thiones 5a-h. The in vitro antitumor activity of the compounds obtained was investigated and the benzothiazol derivatives 6d and 6e showed high effects on leukaemia cell lines CCRF-CEM (CC50 = 12 ± 2 ”mol L1, 8 ± 1 ”mol L1, respectively). These compounds are leading candidates for further development. The title compounds were tested against representatives of several virus families containing single stranded RNA genomes, either positive-sense (ssRNA+), or negative-sense (RNA-), and against double-stranded RNA genomes (dsRNA), as well as some Flaviviridae viruses.U pet reakcijskih koraka sintetizirana je serija novih derivata benzotiazola 6a-h polazeÄi iz supstituiranih fenola preko 1,3,4-oksadiazol-2-tiona 5a-h. Sintetizirani spojevi ispitani su na antitumorsko djelovanje. Benzotiazol derivati 6d i 6e pokazali su jak uÄinak na staniÄnu liniju leukemije CCRF-CEM (CC50 = 12 ± 2, odnosno 8 ± 1 ”mol L1). Ti su spojevi predvodni spojevi za daljnji razvoj. Nadalje, novi su spojevi testirani na djelovanje na nekoliko tipova virusa koji sadrĆŸe bilo pozitivni (ssRNA+) bilo negativni (RNA-) jednolanÄani RNA genom ili dvolanÄani RNA genom (dsRNA), te na neke Flaviviridae viruse
Sintesi e valutazione biologica di nuovi "lead compounds" per la terapia antitubercolare. Derivati del 2-(benzotriazol-1(2)-il)-3- acrilonitrile e delle chinossaline 1,4-diossido
L'insorgenza sempre piĂč elevata di ceppi di M. tuberculosis chemioresistenti ai farmaci abitualmente
impiegati in terapia (MDR) ha spronato la ricerca di nuovi "lead compounds" per lo sviluppo di molecole
che, agendo con meccanismo diverso da quello dei farmaci attualmente impiegati in terapia, possano
contribuire a superare il problema della farmacoresistenza. In quest'ambito le nostre ricerche si sono orientate
verso due differenti direzioni. La prima prende lo spunto dai risultati ottenuti in passato da vari gruppi di
ricerca con alcuni derivati di sintesi di sistemi eterociclici aromatici quali benzimidazolo, benzotiazolo,
benzoisotiazolo e benzofurano, che avevano dimostrato attivitĂ Â antimicobatterica in vitro soprattutto
nei confronti di ceppi MDR.
La seconda linea di ricerca si Ăš basata sulla nota attivitĂ Â antibatterica e soprattutto antimicotica
della chinossalina 1,4-diossido, con la consapevolezza che spesso l'attivitĂ Â antimicobatterica Ăš
associata a quella antifungina
Imidazolo [1,2-a] e 1,2,4-triazolo[4,3-a] chinossaline analoghe degli antifolici metotrexato e trimetrexato
Abbiamo progettato una nuova serie di chinossaline, nelle quali lâanello pirrolico Ăš stato sostituito con unâanello imidazolico
o con uno triazolico lasciando nelle posizioni 2, 5, 6, 7 e 8 dellâanello chinossalinico gli stessi
sostituenti precedentemente esaminati.
Di questi composti verranno descritti la sintesi e i risultati farmacologici relativi alla loro attivitĂ
Synthesis and Biological Evaluation of New 3-Phenyl-1-[(4-arylpiperazin-1-yl)alkyl]-piperidine-2,6-diones
A set of 13 alkyl derivatives of 3-phenylpiperidine-2,6-dione were synthesized. Newly obtained compounds were investigated in vitro against HIV-1 and other selected viruses. The benzyl 3f and fluorophenyl 3g derivatives showed moderate protection against CVB-2 and the compound 3g also against HSV-1. Derivatives were tested also for their antibacterial and antifungal activity. The molecular structures of 3a and 3d were determined by an X-ray analysis
FLOWERED-GeoDBapp: applicazione per mobile basata sui crowd- generating data
Questo studio eÌ parte del progetto H2020 FLOWERED (de-FLuoridation technologies for imprOving quality of WatEr and agRo-animal products along the East African Rift Valley in the context of aDaptation to climate change), coordinato dal Dipartimento di Scienze chimiche e geologiche dellâUniversitaÌ di cagliari, che vede la partecipazione di 14 partner di cui 5 provenienti dalla regione della Rift Valley africana (Etiopia, Kenya e Tanzania). Obiettivo generale del progetto iniziato nel 2016 e di durata triennale, eÌ lo studio nelle tre aree test africane di un sistema di de - fluorizzazione dellâacqua contaminata per cause naturali basato sia su tecnologie adattabili al contesto sociale che su un attento sistema di gestione della risorsa acqua. Pertanto uno degli obiettivi del progetto eÌ il coinvolgimento delle comunitaÌ locali nel processo sia di acquisizione delle conoscenze che di proposta dei sistemi di intervento. In questo ambito eÌ stato proposto lo sviluppo di una piattaforma di condivisione di dati ambientali e socio- economici basata sula raccolta di dati da parte dei tecnici locali. La disponibilitaÌ e diffusione di tecnologie di accesso alla rete internet anche in territori remoti e con particolari condizioni sociali puoÌ consentire pertanto lâutilizzo di strumenti di gestione di dati geografici attraverso esperienze di PPGIS (Public Participation Geographic Information System) e VGI (Voluntary Geographic Information). In questo ambito si inserisce lâapplicazione FLOWERED-GeoDBapp, che attraverso un processo di crowd-generating data intende proporre un sistema di passaggio land cover-land use attraverso il popolamento di un GEO DB basato su una mappa di land cover da classificazione di dati da satellite ad alta risoluzione con dati specifici sullâuso del territorio inseriti localmente. SaraÌ pertanto proposta una legenda di land use basata sulla raccolta di dati non solo di natura ambientale ma anche sociale, culturale ed economica, utilizzando le conoscenze locali e rendendo poi disponibili ai tecnici locali e agli amministratori le informazioni necessarie alla gestione delle risorse e in particolare dellâacqua
Structure-activity relationship studies on new DABOS: effect of substitutions at pyrimidine C-5 and C-6 positions on anti-HIV-1 activity.
Several 5-alkyl, 5-alkenyl, 5-iso-alkyl, 5-halo, 5-aminomethyl and 5-carboxy derivatives of S-DABOs (dihydro-alkyl (or cyclo-alkyl)thio-benzyloxopyrimidines), DATNOs (dihydro-alkylthionaphthylmethyl-oxopyrimidines) and F2-S-DABOs (dihydro-alkyl (or cyclo-alkyl)thio-2,6-difluorobenzyl-oxopyrimidines) have been prepared and tested as anti-HIV-1 agents. S-DABO derivatives bearing at C-6 position monosubstituted phenylmethyl or heteroarylmethyl units have also been synthesized. 2-Alkylthio-3,4-dihydropyrimidin-4(3 H)-one derivatives of F2- S-DABO series bearing small alkyl groups at C-5 proved to be potent inhibitors of HIV-1 replication in vitro with selectivity indexes ranging from 250 to <2500
Antitumor Agents. 2. Synthesis, Structure-Activity Relationships, and Biological Evaluation of Substituted 5H-Pyridophenoxazin-5-ones with Potent Antiproliferative Activity
New antiproliferative compounds, 5H-pyrido[3,2-a]phenoxazin-5-ones (1-10), 5H-benzophenoxazin- 5-one (11), 5H-pyrido[2,3-a]phenoxazin-5-one (12), 5H-pyrido[3,4-a]phenoxazin-5-one
(13), and 5H-pyrido[4,3-a]phenoxazin-5-one (14), were synthesized and evaluated against representative human neoplastic cell lines. The excellent cytotoxic activity of these polycyclic
phenoxazinones, structurally related to the actinomycin chromophore, is discussed in terms of structural changes made to rings A and D (Chart 1). Electron-withdrawing or electron-donating
substituents were introduced at different positions of ring A to probe the electronic and positional effects of the substitution. A nitro group in R2 or in R1 increases the cytotoxic activity,
whereas electron-donating methyl groups in any position lead to 10- to 100-fold decreasing of the activity. The low antiproliferative activity of benzophenoxazinone 11 and pyridophenoxazinones
13 and 14 confirms the crucial role of pyridine nitrogen in the W position of ring D in DNA binding. The unexpected high activity exhibited by 12, which has the nitrogen in the
X position, could be ascribed to a different mechanism of action, which needs further investigation
Synthesis, cytotoxicity and antiviral evaluation of new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives
Linear aromatic N-tricyclic compounds with promising antiviral activity and minimal cytotoxicity were prepared and analyzed in the last years. Specifically, the pyrido[2,3-g]quinoxalinone nucleus was found endowed with high potency against several pathogenic RNA viruses as etiological agents of important veterinary and human pathologies. Following our research program on new antiviral agents we have designed, synthesized and assayed new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives. Lead compounds 1-4 were further modified to enhance their antiviral activity and reduce their cytotoxicity. Thus, different substituents were introduced on N atom at position 1 or the O atom at position 2 of the leads; contextually, several groups were inserted on the nitrogen atom at position 7 of diaminoquinoline intermediates. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against RNA virus families containing single-stranded (either positive-sense (ssRNA+) or negative-sense (ssRNA-)), and double-stranded genomes (dsRNA), and against two representatives of DNA virus families. Some derivatives emerged as potential leads for further development as antiviral agents against some viruses of public health significance, such as RSV, Reo, BVDV and HCV. Particularly, compounds 4, 11b, 11c, 13c, 15a, 18 and 21 resulted active against BVDV at concentrations ranging from 1.3 to 5\ua0\u3bcM. Compound 21 was also evaluated for its activity on the BVDV RdRp. Compound 4 was also tested as potential anti-HCV compound in a subgenomic replication assay. Molecular simulation results provided a molecular rationale for the anti-BVDV activity of these compounds
Haplotype affinities resolve a major component of goat (<i>Capra hircus</i>) MtDNA D-loop diversity and reveal specific features of the Sardinian stock
Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using Bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity.
We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.</br
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