Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position

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Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position. / Popadyuk, Irina I.; Markov, Andrey V.; Morozova, Ekaterina A. и др.

в: Steroids, Том 127, 11.2017, стр. 1-12.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

BibTeX

@article{56dd6e0974d84587be425b6c316b49b5,

title = "Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position",

abstract = "Novel deoxycholic acid (DCA) derivatives were stereoselectively synthesised with –OH and –CH2SR moieties at the C-3 position, where R was a substituted aryl [2-aminophenyl (8) or 4-chlorophenyl (9)] or hetaryl [1-methylimidazolyl (5), 1,2,4-triazolyl (6), 5-amino-1,3,4-thiadiazolyl (7), pyridinyl (10) or pyrimidinyl (11)]. These compounds were prepared in good yields from the C-3β-epoxy derivative 2 in the epoxide ring-opening reaction by S-nucleophiles. These derivatives were evaluated for their in vitro anti-proliferation activity in a panel of tumor cell lines. Data showed that: (i) heterocycle-containing derivatives displayed higher cytotoxicity profiles than the parent molecule; (ii) heterocyclic substituents were more preferable than aryl moieties for enhancing anti-proliferation activity; (iii) the sensitivity of tumor cell lines to analysed compounds decreased in the following order: HuTu-80 (duodenal carcinoma) > KB-3-1 (cervical carcinoma) > HepG2 (hepatocellular carcinoma) > MH-22a (hepatoma); (iv) compounds 5, 6 and 11 exhibited a high cytotoxic selectivity index (HuTu-80: SI > 7.7, 38.5 and 12.0, respectively). Compounds 2 and 6–8 markedly inhibited NO synthesis by interferon γ-induced macrophages. Screening for anti-inflammatory activity of these derivatives in vivo showed their high potency on histamine- (5, 10) and formalin- (2, 10, 11) induced paw edema models.",

keywords = "Anti-inflammatory activity, Antitumor activity, Cytotoxicity, Deoxycholic acid derivatives, Epoxides, Nitric oxide, CHOLIC-ACID, ANTICANCER AGENTS SYNTHESIS, BILE-ACID, DESIGN, DRUG-DELIVERY, URSODEOXYCHOLIC ACID, BIOLOGICAL EVALUATION, NITRIC-OXIDE, ANDROGEN RECEPTOR AFFINITY, CARBONIC-ANHYDRASE INHIBITORS, Humans, Male, Structure-Activity Relationship, Edema/chemically induced, Cell Proliferation/drug effects, Analgesics/chemical synthesis, Chemistry Techniques, Synthetic, Antineoplastic Agents/chemical synthesis, Anti-Inflammatory Agents/chemical synthesis, Animals, Cell Line, Tumor, Mice, Deoxycholic Acid/chemical synthesis, Drug Screening Assays, Antitumor",

author = "Popadyuk, {Irina I.} and Markov, {Andrey V.} and Morozova, {Ekaterina A.} and Babich, {Valeriya O.} and Salomatina, {Oksana V.} and Logashenko, {Evgeniya B.} and Zenkova, {Marina A.} and Tolstikova, {Tat'yana G.} and Salakhutdinov, {Nariman F.}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = nov,

doi = "10.1016/j.steroids.2017.08.016",

language = "English",

volume = "127",

pages = "1--12",

journal = "Steroids",

issn = "0039-128X",

publisher = "Elsevier Science Inc.",

}

RIS

TY - JOUR

T1 - Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position

AU - Popadyuk, Irina I.

AU - Markov, Andrey V.

AU - Morozova, Ekaterina A.

AU - Babich, Valeriya O.

AU - Salomatina, Oksana V.

AU - Logashenko, Evgeniya B.

AU - Zenkova, Marina A.

AU - Tolstikova, Tat'yana G.

AU - Salakhutdinov, Nariman F.

PY - 2017/11

Y1 - 2017/11

N2 - Novel deoxycholic acid (DCA) derivatives were stereoselectively synthesised with –OH and –CH2SR moieties at the C-3 position, where R was a substituted aryl [2-aminophenyl (8) or 4-chlorophenyl (9)] or hetaryl [1-methylimidazolyl (5), 1,2,4-triazolyl (6), 5-amino-1,3,4-thiadiazolyl (7), pyridinyl (10) or pyrimidinyl (11)]. These compounds were prepared in good yields from the C-3β-epoxy derivative 2 in the epoxide ring-opening reaction by S-nucleophiles. These derivatives were evaluated for their in vitro anti-proliferation activity in a panel of tumor cell lines. Data showed that: (i) heterocycle-containing derivatives displayed higher cytotoxicity profiles than the parent molecule; (ii) heterocyclic substituents were more preferable than aryl moieties for enhancing anti-proliferation activity; (iii) the sensitivity of tumor cell lines to analysed compounds decreased in the following order: HuTu-80 (duodenal carcinoma) > KB-3-1 (cervical carcinoma) > HepG2 (hepatocellular carcinoma) > MH-22a (hepatoma); (iv) compounds 5, 6 and 11 exhibited a high cytotoxic selectivity index (HuTu-80: SI > 7.7, 38.5 and 12.0, respectively). Compounds 2 and 6–8 markedly inhibited NO synthesis by interferon γ-induced macrophages. Screening for anti-inflammatory activity of these derivatives in vivo showed their high potency on histamine- (5, 10) and formalin- (2, 10, 11) induced paw edema models.

AB - Novel deoxycholic acid (DCA) derivatives were stereoselectively synthesised with –OH and –CH2SR moieties at the C-3 position, where R was a substituted aryl [2-aminophenyl (8) or 4-chlorophenyl (9)] or hetaryl [1-methylimidazolyl (5), 1,2,4-triazolyl (6), 5-amino-1,3,4-thiadiazolyl (7), pyridinyl (10) or pyrimidinyl (11)]. These compounds were prepared in good yields from the C-3β-epoxy derivative 2 in the epoxide ring-opening reaction by S-nucleophiles. These derivatives were evaluated for their in vitro anti-proliferation activity in a panel of tumor cell lines. Data showed that: (i) heterocycle-containing derivatives displayed higher cytotoxicity profiles than the parent molecule; (ii) heterocyclic substituents were more preferable than aryl moieties for enhancing anti-proliferation activity; (iii) the sensitivity of tumor cell lines to analysed compounds decreased in the following order: HuTu-80 (duodenal carcinoma) > KB-3-1 (cervical carcinoma) > HepG2 (hepatocellular carcinoma) > MH-22a (hepatoma); (iv) compounds 5, 6 and 11 exhibited a high cytotoxic selectivity index (HuTu-80: SI > 7.7, 38.5 and 12.0, respectively). Compounds 2 and 6–8 markedly inhibited NO synthesis by interferon γ-induced macrophages. Screening for anti-inflammatory activity of these derivatives in vivo showed their high potency on histamine- (5, 10) and formalin- (2, 10, 11) induced paw edema models.

KW - Anti-inflammatory activity

KW - Antitumor activity

KW - Cytotoxicity

KW - Deoxycholic acid derivatives

KW - Epoxides

KW - Nitric oxide

KW - CHOLIC-ACID

KW - ANTICANCER AGENTS SYNTHESIS

KW - BILE-ACID

KW - DESIGN

KW - DRUG-DELIVERY

KW - URSODEOXYCHOLIC ACID

KW - BIOLOGICAL EVALUATION

KW - NITRIC-OXIDE

KW - ANDROGEN RECEPTOR AFFINITY

KW - CARBONIC-ANHYDRASE INHIBITORS

KW - Humans

KW - Male

KW - Structure-Activity Relationship

KW - Edema/chemically induced

KW - Cell Proliferation/drug effects

KW - Analgesics/chemical synthesis

KW - Chemistry Techniques, Synthetic

KW - Antineoplastic Agents/chemical synthesis

KW - Anti-Inflammatory Agents/chemical synthesis

KW - Animals

KW - Cell Line, Tumor

KW - Mice

KW - Deoxycholic Acid/chemical synthesis

KW - Drug Screening Assays, Antitumor

UR - http://www.scopus.com/inward/record.url?scp=85029130204&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2017.08.016

DO - 10.1016/j.steroids.2017.08.016

M3 - Article

C2 - 28887170

AN - SCOPUS:85029130204

VL - 127

SP - 1

EP - 12

JO - Steroids

JF - Steroids

SN - 0039-128X

ER -

ID: 9561101