66417-46-7Relevant academic research and scientific papers
Selective AKR1C3 Inhibitors Potentiate Chemotherapeutic Activity in Multiple Acute Myeloid Leukemia (AML) Cell Lines
Verma, Kshitij,Zang, Tianzhu,Gupta, Nehal,Penning, Trevor M.,Trippier, Paul C.
, p. 774 - 779 (2016)
We report the design, synthesis, and evaluation of potent and selective inhibitors of aldo-keto reductase 1C3 (AKR1C3), an important enzyme in the regulatory pathway controlling proliferation, differentiation, and apoptosis in myeloid cells. Combination treatment with the nontoxic AKR1C3 inhibitors and etoposide or daunorubicin in acute myeloid leukemia cell lines, elicits a potent adjuvant effect, potentiating the cytotoxicity of etoposide by up to 6.25-fold and the cytotoxicity of daunorubicin by >10-fold. The results validate AKR1C3 inhibition as a common adjuvant target across multiple AML subtypes. These compounds in coadministration with chemotherapeutics in clinical use enhance therapeutic index and may avail chemotherapy as a treatment option to the pediatric and geriatric population currently unable to tolerate the side effects of cancer drug regimens.
Potent and Highly Selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors Act as Chemotherapeutic Potentiators in Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia
Verma, Kshitij,Zang, Tianzhu,Penning, Trevor M.,Trippier, Paul C.
supporting information, p. 3590 - 3616 (2019/04/26)
Aldo-keto reductase 1C3 (AKR1C3) catalyzes the synthesis of 9α,11β-prostaglandin (PG) F2α and PGF2α prostanoids that sustain the growth of myeloid precursors in the bone marrow. The enzyme is overexpressed in acute myeloid leukemia (
Synthesis and antioxidant activity of caffeic acid derivatives
Sidoryk, Katarzyna,Jaromin, Anna,Filipczak, Nina,Cmoch, Piotr,Cybulski, Marcin
, (2018/09/10)
A series of caffeic acid derivatives were synthesized via a modified Wittig reaction which is a very important tool in organic chemistry for the construction of unsaturated carbon–carbon bonds. All reactions were performed in water medium at 90?C. The aqueous Wittig reaction worked best when one unprotected hydroxyl group was present in the phenyl ring. The olefinations in the aqueous conditions were also conducted with good yields in the presence of two unprotected hydroxyl groups. When the number of the hydroxyl groups was increased to three, the reaction yields were worse, and the derivatives 12, 13, and 18 were obtained with 74%, 37%, and 70% yields, respectively. Nevertheless, the Wittig reaction using water as the essential medium is an elegant one-pot synthesis and a greener method, which can be a safe alternative for implementation in organic chemistry. The obtained compounds were tested for their antioxidant activity, and 12, 13, and 18 showed the highest activities. Moreover, all synthesized compounds displayed no cytotoxicity, and can therefore be used in the pharmaceutical or cosmetic industry.
Antifungal activity of cinnamic acid and benzoic acid esters against Candida albicans strains
Lima, Tamires C.,Ferreira, Alana R.,Silva, Daniele F.,Lima, Edeltrudes O.,de Sousa, Dami?o P.
, p. 572 - 575 (2017/09/30)
Candida albicans is an important opportunistic fungal pathogen capable of provoking infection in humans. In the present study, we evaluated the antifungal effect of 23 ester derivatives of the cinnamic and benzoic acids against 3 C. albicans strains (ATCC-76645, LM-106 and LM-23), as well as discuss their Structure–Activity Relationship (SAR). The antifungal assay results revealed that the screened compounds exhibited different levels of activity depending on structural variation. Among the ester analogues, methyl caffeate (5) and methyl 2-nitrocinnamate (10) were the analogues that presented the best antifungal effect against all C. albicans strains, presenting the same MIC values (MIC?=?128?μg/mL), followed by methyl biphenyl-2-carboxylate (21) (MIC?=?128, 128 and 256?μg/mL for C. albicans LM-106, LM-23, and ATCC-76645, respectively). Our results suggest that certain molecular characteristics are important for the antifungal action.
Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors
Song, Lijun,Merceron, Romain,Gracia, Bego?a,Quintana, Ainhoa Lucía,Risseeuw, Martijn D. P.,Hulpia, Fabian,Cos, Paul,Aínsa, José A.,Munier-Lehmann, Hélène,Savvides, Savvas N.,Van Calenbergh, Serge
, p. 2753 - 2775 (2018/04/23)
In recent years, thymidylate kinase (TMPK), an enzyme indispensable for bacterial DNA biosynthesis, has been pursued for the development of new antibacterial agents including against Mycobacterium tuberculosis, the causative agent for the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous efforts toward the exploration of novel and potent Mycobacterium tuberculosis TMPK (MtTMPK) inhibitors, and reported here the design of a novel series of non-nucleoside inhibitors of MtTMPK. The inhibitors display hitherto unexplored interactions in the active site of MtTMPK, offering new insights into structure-activity relationships. To investigate the discrepancy between enzyme inhibitory activity and the whole-cell activity, experiments with efflux pump inhibitors and efflux pump knockout mutants were performed. The minimum inhibitory concentrations of particular inhibitors increased significantly when determined for the efflux pump mmr knockout mutant, which partly explains the observed dissonance.
HIGHLY SELECTIVE AKR1C3 INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 91; 92, (2018/09/08)
The present invention includes methods and compositions that inhibit AKR1C3 enzymatic activity and consequently reduces androgen receptor (AR) transactivation, AR and prostate specific antigen (PSA) expression levels in, for example, prostate cancer, cast
Synthesis and anticancer activities of glycyrrhetinic acid derivatives
Li, Yang,Feng, Ling,Song, Zhi-Fang,Li, Hai-Bei,Huai, Qi-Yong
, (2016/05/09)
A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 μM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent.
Compositions for the prevention or treatment of neurodegenerative disease containing alkoxyphenylpropenone derivatives or pharmaceutically acceptable salts thereof as an active ingredient
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Paragraph 0399-0402, (2021/05/28)
PURPOSE: An alkoxyphenylpropenone derivative is provided to efficiently use as a pharmaceutical composition for preventing or treating a degenerative brain disease; or pharmaceutical composition for protecting a brain cell by having an excellent protecting effect of the brain cell. CONSTITUTION: An alkoxyphenylpropenone derivative or a pharmaceutically acceptable salt thereof is indicated as below chemical formula 1; and R^1 is hydrogen or O-R^4; R^2 is hydrogen or O-R^5; R^3 is hydroxy, O-R^6 or -NR^7R^8; R^4, R^5 and R^6 are C_1-C_12 straight chain or a side chain alkyl, C_2-C_12 straight chain or a side chain alkenyl, and unsubstituted or C_5-C_6 aryl which is substituted as C_1-C_4 straight chain, or a side chain alkoxy, C_5-C_6 aryl C_1-C_4 alkyl; R^7 is hydrogen, C_1-C_4 straight chain, or a side chain alkyl; R^8 is hydrogen, the C_1-C_4 straight chain or the side chain alkyl, and the C5-C6 aryl which is unsubstituted or hydroxy-substituted, the C1-C4 alkyl or the C5-C6.
A practical, chemoselective approach to O-methylation of carboxylic acids with dimethyl malonate
Mao, Jincheng,Liu, Defu,Li, Yongming,Zhao, Jinzhou,Rong, Guangwei,Yan, Hong,Zhang, Guoqi
, p. 9067 - 9072 (2015/11/09)
A practical and chemoselective method is described for the O-methylation of carboxylic acids. Dimethyl malonate, a low toxic and commercially available compound was found to be an effective methylating reagent for a variety of carboxylic acids affording methyl ester products in good to high yields and with excellent chemoselectivity, without the use of strong bases as additives. A mechanism involving the utilization of potassium bromide is tentatively proposed.
Discovery of the first N -hydroxycinnamamide-based histone deacetylase 1/3 dual inhibitors with potent oral antitumor activity
Li, Xiaoyang,Inks, Elizabeth S.,Li, Xiaoguang,Hou, Jinning,Chou, C. James,Zhang, Jian,Jiang, Yuqi,Zhang, Yingjie,Xu, Wenfang
, p. 3324 - 3341 (2014/05/20)
In our previous study, we designed and synthesized a novel series of N-hydroxycinnamamide-based HDAC inhibitors (HDACIs), among which the representative compound 14a exhibited promising HDACs inhibition and antitumor activity. In this current study, we report the development of a more potent class of N-hydroxycinnamamide-based HDACIs, using 14a as lead, among which, compound 11r gave IC50 values of 11.8, 498.1, 3.9, 2000.8, 5700.4, 308.2, and 900.4 nM for the inhibition of HDAC1, HDAC2, HDAC3, HDAC8, HDAC4, HDAC6, and HDAC11, exhibiting dual HDAC1/3 selectivity. Compounds 11e, 11r, 11w, and 11y showed excellent growth inhibition in multiple tumor cell lines. In vivo antitumor assay in U937 xenograft model identified compound 11r as a potent, orally active HDACI. To the best of our knowledge, this work constitutes the first report of oral active N-hydroxycinnamamide-based HDACIs with dual HDAC1/3 selectivity.
