Synthesis,characterization, DNA interaction studies and anticancer activity of platinum–clotrimazole complexes

New trans-platinum complexes of clotrimazole (CTZ) have been prepared and characterized. Their interaction with DNA and activity against tumour cell lines were evaluated. [Pt (CTZ)₂I₂] (1) was synthesized by the reaction of K₂PtCl₄, KI and CTZ, and [Pt(CTZ)₂Cl₂] (2) by direct reaction of K₂PtCl₄ with CTZ. These complexes were characterized by a combination of elemental analysis, molar conductivity, UV–Vis, IR, and NMR spectroscopy in one and two dimensions. DNA–platinum complex interactions were studied by spectroscopic, thermal denaturation and viscosity titration measurements. Covalent interaction studies were also performed. From these results we suggest that complexes 1 and 2 interact with the minor groove of DNA. Both complexes showed growth inhibitory effects on four out of the six tumour cells lines with GI₅₀ (50% growth inhibition) values in the 5–25 μM range, but there was no indication of cytotoxicity over the range of concentrations tested.     

On P.I. ring and standard identities

An example is given of a ringR (with 1) satisfying the standard identityS ₆[x ₁, ...,x ₆] butM ₂(R), the 2 × 2 matrix ring overR, does not satisfyS ₁₂[x ₁, ...,x ₁₂]. This is in contrast to the caseR=M _n (F),F a field, where by the Amitsur-Levitzki theoremR satisfiesS _2n [x ₁, ...,x _2n] andM ₂(R) satisfiesS _4n [x ₁, ...,x _n]. Part of this work was done while the author enjoyed the hospitality of the University of California at San Diego, the University of Texas at Austin and the University of Washington at Seattle.     

Antibody recognition of chiral surfaces. Enantiomorphous crystals of leucine-leucine-tyrosine

Monoclonal antibodies were selected after immunization with crystals of the tripeptide l-leucine-l-leucine-l-tyrosine. They interact with the tripeptide crystals, but do not interact with the tripeptide molecule, with other crystalline surfaces, or with adsorbed protein. The interactions of two antibodies with crystals of l-Leu-l-Leu-l-Tyr and of its enantiomer d-Leu-d-Leu-d-Tyr were characterized in depth. Antibody 48E is stereoselective and enantioselective: it recognizes only the [011] faces of the l-Leu-l-Leu-l-Tyr crystals, and not the enantiomorphous [011] faces of d-Leu-d-Leu-d-Tyr crystals, or any other faces of either crystal. In contrast, antibody 602E is poorly stereoselective and is not enantioselective: it recognizes the crystals of both enantiomers, interacting with a number of different faces of each. The different recognition patterns are explained on the basis of the nature of the interactions and the structure of the interacting surfaces. Understanding this antibody specificity advances our general understanding of surface recognition and transfer of chiral information across biological interfaces.     

Multicomponent reactions with dihydroazines: efficient synthesis of a diverse set of pyrido-fused tetrahydroquinolines

A multicomponent assembly of pyrido-fused tetrahydroquinolines is accomplished in a one-pot process from the interaction of dihydroazines, aldehydes, and anilines. A rational screening of the different components and parameters of this reaction, such as the range of reactive starting materials, catalysts and reaction conditions (solvent range; thermal, high pressure- and microwave-promoted processes) is carried out. Optimized conditions allow an efficient preparation of pyrido-fused tetrahydroquinolines with good yields, bypassing the biomimetic NADH-like reductive pathway which is typical in the interaction of dihydropyridines with carbonyl compounds and amines. Furthermore, solid-supported versions of the process have been developed, which should facilitate the preparation of libraries.     

Polymeric reagent synthesis of luteinizing hormone-releasing hormone

Luteinizing hormone-releasing hormone, pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂,² was synthesized in a stepwise manner by two approaches: the use of insoluble polymeric active esters derived from (4-hydroxy-3-nitro)benzylated polystyrene and that of solubleN,N-dicyclohexylcarbodiimide. The overall yields of the syntheses were 40 and 7%, respectively. The efficiencies of the two synthetic routes, in which identical intermediate peptides were prepared, are compared.     

N-acylazinium salts: a new source of iminium ions for Ugi-type processes

A multicomponent reaction involving the interaction of azines (quinolines, isoquinolines, and phenanthridine) with activating agents (chloroformates, acid halides, and sulfonyl halides), isocyanides, and water is described. The products of this process, alpha-carbamoylated-1,2-dihydroazines, are the result of the addition of the isocyanide partner to the N-acylazinium salt formed in situ. This represents a new source of iminium ion equivalents for Ugi-type reactions.