I. Sestili

Synthesis and antirhinovirus activity of cyano and amidino substituted flavanoids

Abstract Cyano and amidino flavans, isoflavans and 3(2H)-isoflavenes were synthesized in order to study their in vitro antirhino-virus activity, by comparison with the known corresponding chloro derivatives. The activity of the new compounds was evaluated on rhinovirus 1 B infected HeLa cell cultures by examining their ability to interfere with viral cytopathic effect and with plaque formation. It was found that generally the cyano derivatives behave like the chloro compounds, whereas the amidino derivatives show a lower activity, although always dependent on the position of substituent.

Synthesis and evaluation of anti-rhinovirus 1B activity of oxazolinyl-isoflavans and -3(2H)-isoflavenes

Oxazolinyl-isoflavans and −3(2H)-isoflavenes, substituted or not with a chlorine atom, were synthesized in order to compare their anti-rhinovirus activity with that of previously studied analogous compounds. The activity of the oxazolines and of the esters and acids, which are intermediates in the synthesis, was studied in vitro against rhinovirus serotype 1B infection in HeLa cells. The ability of various non cytotoxic concentrations to interfere with the development of the viral cytopathic effect and plaque formation was examined. All the tested compounds exerted a significant antiviral activity, and most of them were as active as some representative compounds of the oxazolinyl-phenoxyalkylisoxazole (WIN) series. 6-Oxazolinylisoflavan (VI) appeared to be the most interesting compound due to its high activity and therapeutic index. Among the substituted isoflavans and isoflavenes tested so far, the intermediate compound 6-chloro-3 (2H)-isoflavene-4′-carboxylic acid (XIX) was unexpectedly the most potent inhibitor of rhinovirus 1B plaque formation.

LTB4 as marker of 5-LO inhibitory activity of two new N-ω-ethoxycarbonyl-4-quinolones

The supposed 5-LO inhibitory activity of two N-ω-ethoxycarbonyl-4-quinolones was tested determining leukotriene B4 (LTB4) in RBL-1 cell cultures, pretreated with the two compounds of interest. LTB4, obtained by solid-phase extraction (SPE) from celle cultures supernatants, was determined by micellar electrokinetic chromatography (MEKC). The analysis was performed using an uncoated capillary, filled with borate buffer at pH 8.3, containing 12.5 mM SDS as micelles generator. Therefore, following the decreasing of LTB4 it was possible to verify the 5-LO inhibitory activity of two quinolone derivatives. To asses the suitability of the use of LTB4 as marker of the activity of the new compounds, the analysis was repeated using quercetin, a well known 5-LO inhibitor.

Guanylhydrazones of 3-substituted 2-pyridinecarboxaldehyde and of (2-substituted 3-pyridinyloxy) acetaldehyde as prostanoid biosynthesis and platelet aggregation inhibitors

Abstract Some guanylhydrazones of (3-benzyloxy)-2-pyridinecarboxaldehyde and of (2-substituted 3-pyridinyloxy)acetaldehyde were prepared in order to evaluate their possible activity as inhibitors of prostanoid biosynthesis in human serum. Only those products of the second group without the carboxylic function reduced prostanoid generation in vitro at the highest concentration; they also inhibited platelet aggregation induced by arachidonic acid and U-46619. The results suggest that these compounds are both inhibitors of cyclooxygenase and cyclic endoperoxides/TxA 2 platelet receptor antagonists.

In vitro Evaluation of the Anti-Picornavirus Activities of New Synthetic Flavonoids

Substituted oxazolinylflavons and oxazolinylflavanones were synthesized in order to compare their anti-picornavirus activities with those of related natural and synthetic compounds. The antiviral potencies of the new compounds were evaluated against rhino-virus type 1B and poliovirus type 2 by a plaque reduction assay in HeLa cell cultures. Among the substituted flavanones only 6-chloro-4′-oxazolinylflavanone showed activity against both viruses. A comparison of the effects of 3-substituted flavones indicated that the presence of a 3-methoxy group enhances the activity against rhinovirus, while the presence of a 3-hydroxy group enhances the activity against poliovirus.

Synthesis and anti-rhinovirus 1B activity of oxazolinylflavans

Two series of flavans were synthesized, the first substittued at 4′ and/or 6 position with chlorine and cyano groups, and the second one with chlorine and/or oxazoline rings. The new compounds were tested in vitro against human rhinovirus 1B (HRV 1B) infection of HeLa cells by measuring the effect on the development of viral cytopathic effect and plaque formation. The compounds including both chlorine and cyano groups were the most active; 4′-(4,5-dihydro-2-oxazolyl)-6-chloroflavan was the most potent inhibitor among the oxazoline derivatives.

Synthesis and anti-human immunodeficiency virus type 1 integrase activity of hydroxybenzoic and hydroxycinnamic acid flavon-3-yl esters

A series of new hydroxybenzoic and hydroxycinnamic acid flavon-3-yl esters were synthesized in order to obtain compounds targeting the human immunodeficiency virus (HIV) type 1 integrase (IN). The esters were tested for anti-IN and anti-reverse transcriptase (RT) activity in enzyme assays and for anti-HIV-1, anti-proliferative and anti-topoisomerase activity in cell-based assays. In enzyme assays, the two gallic acid flavon-3-yl esters showed a notable IN inhibition (IC50 values were 8.3 and 9.1 µM, respectively), while the two caffeic acid flavon-3-yl esters exhibited a modest activity (IC50 75 and 60 µM, respectively). Replacement of hydroxyl groups resulted in loss of potency. Caffeic acid 3′,4′-dichloroflavon-3-yl ester also inhibited the RT activity whereas it was not active on human topoisomerases. It therefore represents an interesting example of a compound specifically targeting more than one step of the virus replication cycle.