Structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: Design, synthesis, lipophilicity and biological activity

Publication date: 15 April 2020Source: Journal of Molecular Structure, Volume 1206Author(s): Imre Huber, Zsuzsanna Rozmer, Zoltán Gyöngyi, Ferenc Budán, Péter Horváth, Eszter Kiss, Pál PerjésiAbstractThe chemical susceptibility of the β-diketone linker between the two aromatic rings in the structure of curcumin to hydrolysis and metabolism has made it crucial to investigate structurally modified analogs of curcumin without such shortcomings. The synthesis of twenty cyclic C5-curcuminoids is described in this study in order to gain more insight into their anticancer structure-activity relationship (SAR). The design of their synthesis included four different cyclanones and five substituted aromatic aldehydes to form four, five-membered subgroups. These model compounds were evaluated in vitro for antiproliferative activity in an XTT cell viability assay against MCF-7 human non-invasive breast adenocarcinoma cancer cells and Jurkat human T lymphocyte leukemia cells in five different concentrations (10 nM, 100 nM, 1 μM, 10 μM and 20 μM). The majority of the compounds investigated have shown remarkable cytotoxicity with IC50 values in the range of 120 nM and 2 μM with very high relative toxicity values to curcumin. The SAR conclusions are drawn and summarized. A method was developed and applied in a TLC based experimental logP measurement, which is new for such C5-curcuminoids. T...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research

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In conclusion, the roles of basophils in experimental and human cancers have been little investigated and remain largely unknown. The elucidation of the roles of basophils in tumor immunity will demand studies on increasing complexity beyond those assessing basophil density and their microlocalization in TME. There are several fundamental questions to be addressed in experimental models and clinical studies before we understand whether basophils are an ally, adversary, or even innocent bystanders in cancers. PMID: 32036602 [PubMed - in process]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
In conclusion, our preclinical results suggest that CD44v6.CAR T based adoptive therapy could be a promising strategy in solid cancer treatment.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
i Lannang A Abstract One new tirucallan derivative, leutcharic acid (1) was isolated from Stereospermum acuminatissimum stem bark together with the known compounds 3-oxo-22-hydroxyhopane (2), 3,4-secotirucalla-4(28),7,24-trien-3,21-dioic acid (3), 3-oxotirucalla-7,24-dien-21-oic acid (7), lupeol (4), β-sitosterol (5) and stigmasterol (6). The structures of the isolated compounds were elucidated using 1 D and 2 D NMR spectroscopy in combination with literature data. To the best of our knowledge, this is the first report on the cytotoxic properties' constituents of S. acuminatissimum. Cytotoxicity...
Source: Natural Product Research - Category: Biochemistry Authors: Tags: Nat Prod Res Source Type: research
Molecules, Vol. 25, Pages 88: The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity Molecules doi: 10.3390/molecules25010088 Authors: Izabela Jęśkowiak Stanisław Ryng Marta Świtalska Joanna Wietrzyk Iwona Bryndal Tadeusz Lis Marcin Mączyński Thanks to the progress in oncology, pharmacological treatment of cancer is gaining in importance and in the near future anti-cancer chemotherapeutics are expected to be the main method of treatment for cancer diseases. What is more, the search for new anti-cancer compounds with the desi...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
ConclusionsOverall, our data demonstrate for the first time that low [Na+] promotes cancer progression in vitro, thus suggesting that hyponatremia is not a simple bystander of disease severity in cancer.
Source: Endocrine - Category: Endocrinology Source Type: research
Conclusions: The 5-year OS of patients with stage III NSCLC treated with CRT was in keeping with survival figures reported from prospective clinical trials. There is, however, significant morbidity associated with long-term survival and this should be taken into account when making informed treatment decisions. PMID: 31737309 [PubMed]
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
Abstract To understand the androgen receptor (AR) in different human malignancies, we conducted a pan-cancer analysis of AR in different tumor tissues and association with patient survival and obtained AR expression data from The Cancer Genome Atlas. Pan-Cancer Analysis of AR indicated that 12 tumor types had decreased AR expression in the tumor, while glioblastoma multiforme has overexpressed AR. The survival analysis showed that high AR mRNA is associated with poor survival of stomach adenocarcinoma and low-grade glioma, but better survival of adrenocortical carcinoma, kidney renal clear cell carcinoma, acute my...
Source: Genomics - Category: Genetics & Stem Cells Authors: Tags: Genomics Source Type: research
Abstract The Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is among long non-coding RNAs (lncRNAs) which has disapproved the old term of "junk DNA" which was used for majority of human genome which are not transcribed to proteins. An extensive portion of literature points to the fundamental role of this lncRNA in tumorigenesis process of diverse cancers ranging from solid tumors to leukemia. Being firstly identified in lung cancer, it has prognostic and diagnostic values in several cancer types. Consistent with the proposed oncogenic roles for this lncRNA, most of studies have shown up-...
Source: Experimental and Molecular Pathology - Category: Pathology Authors: Tags: Exp Mol Pathol Source Type: research
ski A Abstract The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, in this paper, we describe the synthesis of a new class of SAL analogs that combine key modifications at the C1 and C20 positions. The activity of the obtained SAL derivatives was evaluated using primary acute lymphoblastic leukemia, human breast adenocarcinoma and normal mammary epithel...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
Abstract Immunological principles based on Treg cell self-stabilization and the discovery that tumors are capable of evading the body's defense mechanism have led to more effective immuno-oncology therapies. Hence, next generation immunotherapy can only be effective if researchers have an in-depth understanding of the function and regulation of Treg cells in antitumor immunity combined with the discovery of new immunity targets. This can enhance clinical efficacy of future and novel therapies and reduces any adverse reactions arising from the latter. This review of the literature discusses tumor treatment strategi...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
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