Silvana Casati

Co‐administration of ibuprofen and nitric oxide is an effective experimental therapy for muscular dystrophy, with immediate applicability to humans

Background and purpose:  Current therapies for muscular dystrophy are based on corticosteroids. Significant side effects associated with these therapies have prompted several studies aimed at identifying possible alternative strategies. As inflammation and defects of nitric oxide (NO) generation are key pathogenic events in muscular dystrophies, we have studied the effects of combining the NO donor isosorbide dinitrate (ISDN) and the non‐steroidal anti‐inflammatory drug ibuprofen.

Selective enzymatic transformations of itaconic acid derivatives: An access to potentially useful building blocks

Abstract Hydrolytic enzymes regioselectively catalyze the hydrolysis of diethyl itaconate 5a to the monoester 5c and opening of itaconic anhydride 6 to the regioisomeric monoester 5b that was tranformed into the hydroxy esters 2. This was used for the synthesis of β-methylene-,γ-butyrolactone 7 and of the racemic epoxyalcohol 3, that was resolved by a highly enantioselective Pseudomonas fluorescens lipase-catalyzed transesterification into (S)-3 and (S)-8 (90 and 86% ee, respectively).

The Action of Adenosine Deaminase (E.C. 3.5.4.4.) on Adenosine and Deoxyadenosine Acetates: The Crucial Role of the 5′-Hydroxy Group for the Enzyme Activity

Abstract From adenosine 1 , 2′-deoxyadenosine 3 and 3′-deoxyadenosine 5 all the acetates were prepared by lipase-catalyzed reactions. Only the acetates with free 5′-hydroxy group were deaminated by adenosine deaminase (ADA), confirming the crucial role of 5′-OH for the enzyme activity.

N6-Alkyladenosines: Synthesis and evaluation of in vitro anticancer activity

A series of adenosine analogues differently substituted in N⁶-position were synthesized to continue our studies on the relationships between structure and biological activity of iPA. The structures of the compounds were confirmed by standard studies of ¹H NMR, MS and elemental analysis. These molecules were then evaluated for their anti-proliferative activity on bladder cancer cells. We found that some of these compounds possess anti-proliferative activity but have no effect on cell invasion and metalloprotease activity.

An Insight into the Active Site of Pseudomonas Fluorecens (P. cepacia) Lipase to Define the Stereochemical Demand for the Transesterification in Organic Solvents

The Pseudomonas fluorescens lipase-catalyzed transesterification of 2-methyl alkanols 1 and the 2-substituted oxiranemethanols 2 with vinyl acetate in organic solvents has been studied and the results discussed in terms of steric and electronic demand within the recently postulated models of the lipase active site.

Regioselective Hydrolysis of Diacetoxynaphthalenes Catalyzed by Pseudomonas sp. Lipase in an Organic Solvent

Abstract Depending on the relative positions of the acetyl groups in the aromatic rings, the Pseudomonas sp. lipase-catalyzed hydrolysis of diacetoxynaphthalenes in tert-butylmethyl ether proceeds regioselectively to afford the corresponding monoacetates.

Studies on the regio- and enantioselectivity of the lipase-catalyzed transesterification of 1′- and 2′-naphthyl alcohols in organic solvent

The Pseudomonas cepacia lipase preferentially acylates the 2′-regioisomers of a few 1′- and 2′-naphthyl alcohols; in the case of compounds 3a, 3c, 4a, 4c the (R)-alcohols (65→98% ee) and the (S)-acetates (62–98% ee) are formed.

Baker's yeast-mediated hydrogenation of 2-substituted allyl alcohols: A biocatalytic route to a new highly enantioselective synthesis of (R)-2-methyl alkanols

Abstract The biohydrogenation of 2-substituted allyl alcohols 1a-c proceeds enantioselectively (95–98% ee) to afford (R)-2-methyl alkanols 2a-c.

Lipase-catalyzed monoprotection of 1,4-diols in an organic solvent using vinyl benzoate as acyl transfer agent

Lipase from Mucor miehei (MML) has been selected as the most suitable enzyme to catalyze the efficient monobenzoylation of 1,4-diols using vinyl benzoate as acyl transfer reagent in tert-butyl methyl ether. The regioselectivity of the monobenzoylation of 2-substituted-1,4-diols has been studied as well.

N6-Isopentenyladenosine and its Analogue N6-Benzyladenosine Induce Cell Cycle Arrest and Apoptosis in Bladder Carcinoma T24 Cells

Cytokinins are phytohormones critically involved in the regulation of plant growth and development. They also affect the proliferation and differentiation of animal cells, thus representing new tools to treat diseases that involve dysfunctional cell growth and/or differentiation. Recently, by performing structure-function studies on human cells, we found that only N6-isopentenyladenosine and its benzyl analogue N6-benzyladenosine suppress the clonogenic activity and the growth of different neoplastic cells. We here broaden our studies on bladder carcinoma T24 cells, because, due to the high recurrence rate of bladder cancer, new active molecules are sought to contrast the growth of this tumor. Early events induced by N6-isopentenyladenosine and N6-benzyladenosine are the alteration of T24 cell morphology and the disorganization of the actin cytoskeleton. After 24 h N6-isopentenyladenosine and N6-benzyladenosine inhibit growth by arresting the cells in the G0/G1 phase of the cell cycle. We also show that the two compounds induce apoptosis, an event linked to the activation of caspase 3. Since DNA damage is a prime factor resulting in cell cycle arrest and apoptosis, it is noteworthy that we do not detect any genotoxic effect upon treatment of T24 cells with N6-isopentenyladenosine and N6- benzyladenosine. Because the disruption of actin filaments leads to G1 arrest and is also implicated in apoptosis, we hypothesize that cytoskeletal rearrangement might be responsible for triggering the antiproliferative and proapotpotic effects of N6-isopentenyladenosine and N6- benzyladenosine in T24 cells.