10 research outputs found
Structural analysis and biomedical potential of novel salicyloyloxy estrane derivatives synthesized by microwave irradiation
SCIENTIFIC WORK SYNTHESIS OF SOME 16,17-SECO- ANDROST-5-ENE DERIVATIVES
16,17-secoandrost-5-ene-16-nitrile (4) was synthesized by a three-stage procedure. First, the formyl group of compound 1 was reduced, to yield the alcohol 2. Compound 2 was further transformed to the mesyloxy derivative 3, whose reduction with NaBH 3CN gave compound 4. Apart from compound 4 as the main reaction product, two additional products were obtained, for which the GC/MS analysis suggested that they are Ī 8(14) and Ī 14 derivatives of compound 4. Compound 4 was transformed into 3Ī²-hydroxy-16,17-secoandrost-5-ene-16-nitrile (7), the Oppenauer oxidation of which afforded 3-oxo-16,17-secoandrost-4-ene-16-nitrile (8). UDC 547.92.057:615.2 DOI: 10.2298/HEMIND100212009G There are various ways of reducing the C=O group of aldehydes and ketones to a CH2 [1]. The two oldest methods are the WolffāKishner reduction and the Clemensen reduction. In the WolffāKishner reduction, the aldehyde or ketone is heated with hydrazine hydrate an
SYNTHESIS AND CYTOTOXIC ACTIVITY OF A SERIES OF BILE ACID DERIVATIVES
The new conjugates of selected bile acids (hyocholic (2), deoxycholic (3), hyodeoxycholic (4) and 12-ketocholic (5) acids) with ethyl 11-aminoundecanoate 7, 8, 11, and 13 were synthesized. The conjugation reaction was carried out in ethyl acetate in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and triethylamine. Under the same experimental conditions, the conjugation reaction involving ethyl 6-aminohexanoate resulted in formation of a conjugate 9 only in the case of deoxycholic acid (3) in addition to the unexpected ethyl ester 10. In the case of the other bile acids (cholic (1), hyodeoxycholic (4) and 12-ketocholic (5) acids) only an unexpected ester formation took place giving esters 6, 12, and 14. Cytotoxic activity against four tumor cell lines (human breast adenocarcinoma ER-, MDA-MB-231; breast adenocarcinoma ER+, MCF-7; cervix epiteloid carcinoma, HeLa S-3; and prostate cancer, PC-3) was evaluated. Conjugate 8 showed strong activity against HeLa S-3 and conjugate 11 for PC-3. Ethyl ester of 12-ketocholic acid 14 showed very strong antiproliferative activity against MCF-7 and HeLa S-3. Studies of bile acids, their physiology and metabolism
Estimation of chromatographic lipophilicity of some D-homo androstene derivatives
Quantitative structure-retention relationship (QSRR) method was applied to
study the chromatographic behaviour of D-homo-androstene derivatives 1-7.
Retention constants (RM 0) of the analysed derivatives were determined by
reversed-phase high-performance thin-layer chromatography (RP HPTLC) on C18
plates by using four mobile phase mixtures: methanol-water, acetone-water,
acetonitrile-water, and dioxane-water. Correlation analysis based on multiple
regression method was applied in order to model chromatographic retention by
means of nine different lipophilicity descriptors (logP). The developed QSRR
models were cross-validated and high-quality validation parameters were
obtained by leave-one-out method. It was found that the derived QSRR models
have a good predictive ability. [Projekat Ministarstva nauke Republike
Srbije, br. 172012 i br. 172014
Selective antitumour activity and ER[alpha] molecular docking studies of newly synthesized d-homo fused steroidal tetrazoles
X-ray structural analysis, antioxidant and cytotoxic activity of newly synthesized salicylic acid derivatives
New salicylic (2-hydroxybenzoic) acid derivatives 1ā6 were prepared by conventional heating or microwave irradiation of a mixture consisting of methyl salicylate and the corresponding amino alcohol (2,2'-dihydroxydiethylamine, 2,2',2?-trihydroxytriethylamine or N-phenyl-2,2'-dihydroxydiethylamine) and metallic sodium as catalyst. For compounds 1, 3, and 5 X-ray structure analysis was performed, as well as molecular mechanics calculations (MMC), to define their conformation in terms of their energy minima. Comparison of crystal and MMC structures for these three compounds (1, 3, and 5) revealed that the intramolecular hydrogen bonds play an important role, stabilizing conformation of the most part of the molecule. The antioxidant activity and cytotoxicity of the synthesized derivatives were evaluated in a series of in vitro tests. The newly synthesized compounds exhibited strong activity against hydroxyl radical, as well as promising lipid peroxidation inhibition. The study showed that the electronic effects of the groups at the N atom are responsible for neutralization of the OH radical, i.e., antioxidant activity. Compounds 1ā3 exhibited sub-micromolar cytotoxicity against HeLa S3, whereas compounds 1, 3 and 5 efficiently inhibited the growth of PC3 cells