scholarly journals Synthesis and anticancer activity of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides against PC-3 prostate cancer cells

2019 ◽  
Vol 13 (5) ◽  
pp. 331-337
Author(s):  
S. A. Demchenko ◽  
Yu. A. Fedchenkova ◽  
T. А. Bukhtiarova ◽  
L. S. Bobkova ◽  
V. V. Sukhoveev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Carboxylic Acid ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Quaternary Salt ◽  
In Vitro Test ◽  
Prostate Cancer Cells ◽  
Naoh Solution ◽  
Acid Arylamides

Pharmacotherapy of prostate cancer is an important part in combating oncologic diseases. This is very relevant, because prostate cancer is a cause of 10 % of deaths from all cancerous diseases in males. The aim of the study – to synthesize novel derivatives of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides and to evaluate their antitumor activity against PC-3 prostate cancer cells. By reaction of equimolar amounts of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine with a-amino-4-chloroacetophenone chlorohydrate, 3-(4-chlorophenyl)-6,7,8,9- tetrahydro-5Н-imidazo[1,2-a]azepine was synthesized. By alkylation of a-bromo-4-іsopropylacetophenone in ethylacetate and following treatment of the obtained intermediary quaternary salt with excess of 5 % NaOH solution,1-(41-isopropylphenyl)-4-(42chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd] azulene was synthesized. By boiling it with equimolar amounts of correspondding arylisocyanates in dried benzol, an array of 1-(41-iso propylphenyl)-4(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides were synthesized. Structure and purity of all compounds obtained were confirmed by data of MR1Н spectroscopy. Lipophilicity (LogP) of compounds 6 and 8 a-i was calculated with the ACD LogP program. Antitumor activity of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid (3-methylphenyl) and (3-methoxyphenyl)-amides was evaluated at in vitro test on prostate cancer PC-3 cell lines. It is indicated, that at concentration of 10–5 M these compounds exceed 5-fluorouracil as comparison drug in inhibiting PC-3 prostate cancer cells growth by 52.32 % and 3.93 % correspondingly. The data obtained substantiate feasibility of further studies of 1-(41-isopro pylphenyl)-4-(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd] azulene-2-carboxylic acid arylamides as new, potential antitumor medicines for prostate cancer treatment.

scholarly journals Synthesis and anticancer activity of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)5,6,7,8-tetrahydro-2,4a-diazacyclopenta[ cd ]azulene-2-carboxylic acid arylamides against PC-3 prostate cancer cells

2019 ◽  
Vol 13 (5) ◽  
Author(s):  
S. A. Demchenko ◽  
Yu. A. Fedchenkova ◽  
T. A. Bukhtiarova ◽  
L. S. Bobkova ◽  
V. V. Sukhoveev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Carboxylic Acid ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Quaternary Salt ◽  
In Vitro Test ◽  
Prostate Cancer Cells ◽  
Naoh Solution ◽  
Acid Arylamides

Pharmacotherapy of prostate cancer is an important part in combating oncologic diseases. This is very relevant, because prostate cancer is a cause of 10 % of deaths from all cancerous diseases in males. The aim of the study – to synthesize novel derivatives of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides and to evaluate their antitumor activity against PC-3 prostate cancer cells. By reaction of equimolar amounts of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine with a-amino-4-chloroacetophenone chlorohydrate, 3-(4-chlorophenyl)-6,7,8,9- tetrahydro-5Н-imidazo[1,2-a]azepine was synthesized. By alkylation of a-bromo-4-іsopropylacetophenone in ethylacetate and following treatment of the obtained intermediary quaternary salt with excess of 5 % NaOH solution,1-(41-isopropylphenyl)-4-(42chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd] azulene was synthesized. By boiling it with equimolar amounts of correspondding arylisocyanates in dried benzol, an array of 1-(41-iso propylphenyl)-4(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides were synthesized. Structure and purity of all compounds obtained were confirmed by data of MR1Н spectroscopy. Lipophilicity (LogP) of compounds 6 and 8 a-i was calculated with the ACD LogP program. Antitumor activity of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid (3-methylphenyl) and (3-methoxyphenyl)-amides was evaluated at in vitro test on prostate cancer PC-3 cell lines. It is indicated, that at concentration of 10–5 M these compounds exceed 5-fluorouracil as comparison drug in inhibiting PC-3 prostate cancer cells growth by 52.32 % and 3.93 % correspondingly. The data obtained substantiate feasibility of further studies of 1-(41-isopro pylphenyl)-4-(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd] azulene-2-carboxylic acid arylamides as new, potential antitumor medicines for prostate cancer treatment.

scholarly journals Retigeric Acid B Exhibits Antitumor Activity through Suppression of Nuclear Factor-κB Signaling in Prostate Cancer Cells in Vitro and in Vivo

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e38000 ◽  
Author(s):  
Yong-Qing Liu ◽  
Xiao-Yan Hu ◽  
Tao Lu ◽  
Yan-Na Cheng ◽  
Charles Y. F. Young ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Prostate Cancer Cells

scholarly journals Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo

2017 ◽  
Vol 7 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Guangyao Lv ◽  
Dengjun Sun ◽  
Jingwen Zhang ◽  
Xiaoxia Xie ◽  
Xiaoqiong Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Arg-Gly-Asp (RGD)-Modified E1A/E1B Double Mutant Adenovirus Enhances Antitumor Activity in Prostate Cancer Cells In Vitro and in Mice

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147173 ◽  
Author(s):  
Yue-Hong Shen ◽  
Fei Yang ◽  
Hua Wang ◽  
Zhi-Jian Cai ◽  
Yi-Peng Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Double Mutant ◽  
Prostate Cancer Cells

scholarly journals Riccardin D Exerts Its Antitumor Activity by Inducing DNA Damage in PC-3 Prostate Cancer Cells In Vitro and In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74387 ◽  
Author(s):  
Zhongyi Hu ◽  
Feng Kong ◽  
Manfei Si ◽  
Keli Tian ◽  
Lin Xi Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3975
Author(s):  
Marco A. De Velasco ◽  
Yurie Kura ◽  
Naomi Ando ◽  
Noriko Sako ◽  
Eri Banno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Late Stage ◽  
Early Stage ◽  
Castration Resistant Prostate Cancer ◽  
Akt Inhibitor ◽  
Molecular Features ◽  
Context Specific

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

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