New Boron Containing Acridines: Synthesis and Preliminary Biological Study.

The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with N3CH2CH2NH2, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles. DNA interaction studies via absorbance spectroscopy showed the weak binding of the obtained conjugates with DNA. The antiproliferative activity (IC50) of the boronated conjugates against a series of human cell lines was evaluated through an MTT assay. The results suggested that acridine derivatives of cobalt bis(dicarbollide) might serve as a novel scaffold for the future development of new agents for boron neutron capture therapy (BNCT).

Synthesis of Cobalt Bis(Dicarbollide)-Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy.

A series of novel cobalt bis(dicarbollide)-curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)-curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).

Synthesis and Antibacterial Activity Studies of the Conjugates of Curcumin with closo-Dodecaborate and Cobalt Bis(Dicarbollide) Boron Clusters.

A series of novel conjugates of cobalt bis(dicarbollide) and closo-dodecaborate with curcumin were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition. These conjugates were tested for antibacterial activity. It was shown that all derivatives are active when exposed to Bacillus cereus ATCC 10702 and are not active against Gram-negative microorganisms and Candida albicans at the maximum studied concentration of 1000 mg/L. The conjugate of alkynyl-curcumin with azide synthesized from the tetrahydropyran derivative of cobalt bis(dicarbollide) exhibited activity against Gram-positive microorganisms: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and the clinical isolate MRSA 17, that surpassed curcumin by 2-4 times.

Synthesis of Zwitter-Ionic Conjugate of Nido-Carborane with Cholesterol.

9-HC≡CCH2Me2N-nido-7,8-C2B9H11, a previously described carboranyl terminal alkyne, was used for the copper(I)-catalyzed azide-alkyne cycloaddition with azido-3ß-cholesterol to form a novel zwitter-ionic conjugate of nido-carborane with cholesterol, bearing a 1,2,3-triazol fragment. The conjugate of nido-carborane with cholesterol, containing a charge-compensated group in the linker, can be used as a precursor for the preparation of liposomes for BNCT (Boron Neutron Capture Therapy). The solid-state molecular structure of a nido-carborane derivative with the 9-Me2N(CH2)2Me2N-nido-7,8-C2B9H11 terminal dimethylamino group was determined by single-crystal X-ray diffraction.

Synthesis and Structure of Nido-Carboranyl Azide and Its "Click" Reactions.

Novel zwitter-ionic nido-carboranyl azide 9-N3(CH2)3Me2N-nido-7,8-C2B9H11 was prepared by the reaction of 9-Cl(CH2)3Me2N-nido-7,8-C2B9H11 with NaN3. The solid-state molecular structure of nido-carboranyl azide was determined by single-crystal X-ray diffraction. 9-N3(CH2)3Me2N-nido-7,8-C2B9H11 was used for the copper(I)-catalyzed azide-alkyne cycloaddition with phenylacetylene, alkynyl-3ß-cholesterol and cobalt/iron bis(dicarbollide) terminal alkynes to form the target 1,2,3-triazoles. The nido-carborane-cholesterol conjugate 9-3ß-Chol-O(CH2)C-CH-N3(CH2)3Me2N-nido-7,8-C2B9H11 with charge-compensated group in a linker can be used as a precursor for preparation of liposomes for Boron Neutron Capture Therapy (BNCT). A series of novel zwitter-ionic boron-enriched cluster compounds bearing a 1,2,3-triazol-metallacarborane-carborane conjugated system was synthesized. Prepared conjugates contain a large amount of boron atom in the biomolecule and potentially can be used for BNCT.