Search results for "Neoplastic"
showing 10 items of 2901 documents
Indole Diterpenoids from an Endophytic Penicillium sp.
2019
A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots of the medicinal plant Zingiber officinale, yielded nine new indole diterpenoids (1-9), together with 13 known congeners (10-22). The structures of the new compounds were elucidated by 1D and 2D NMR analysis in combination with HRESIMS data. The absolute configuration of the new natural products 1, 3, and 7 was determined using the TDDFT-ECD approach and confirmed for 1 by single-crystal X-ray determination through anomalous dispersion. The isolated compounds were tested for cytotoxicity against L5178Y, A2780, J82, and HEK-293 cell lines. Compound 1 was the most active metabolite toward L5178Y ce…
Porphyrin and phthalocyanine photosensitizers designed for targeted photodynamic therapy of colorectal cancer
2020
Colorectal cancer is of particular concern due to its high mortality rate count. Recent investigations on targeted phototherapy involving novel photosensitizers and drug-delivery systems have provided promising results and realistic prospects for a successful medical treatment. New research trends have been focused particularly on development of advanced molecular systems offering effective photoactive species which could be selectively delivered directly into the affected cells. Porphyrins and phthalocyanines have been considered extremely attractive for this purpose due to their molecular versatility, excellent photochemical properties and multifunctional nature. In this review it has bee…
Synthesis and Antitumor Activity of 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-indoles and 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-7-azaindoles
2011
Given the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4-bis(3'-indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl-7-azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α-bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ∼60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exh…
A Facile Synthesis of Deaza-Analogues of the Bisindole Marine Alkaloid Topsentin
2013
A series of substituted ethyl 1-[(tert-butoxycarbonyl)amino]-2-methyl-5- (1-methyl-1H-indol-3-yl)-4-[(1-methyl-1H-indol-3-yl)carbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98%) by one-pot reactions between β-dicarbonyl compounds 12a-e and 1,2-diaza-1,3-diene (DD) 13. Derivatives 10a,c-e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA) in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-p…
Molecular modeling approaches in the discovery of new drugs for anti-cancer therapy: the investigation of p53-MDM2 interaction and its inhibition by …
2010
The mdm2 oncogene product, MDM2, is an ubiquitin protein ligase that inhibits the transcriptional activity of the tumor suppressor p53 and promotes its degradation. About 50% of all human cancers present mutations or deletions in the TP53 gene. In the remaining half of all human neoplasias that express the wild-type protein, aberrations of p53 regula- tors, such as MDM2, account for p53 inhibition. For this reason, designing small-molecule inhibitors of the p53-MDM2 protein-protein interaction is a promising strategy for the treatment of cancers retaining wild-type p53. The development of inhibitors has been challenging. Although many small-molecule MDM2 inhibitors have shown potent in vitr…
A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells
2021
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4…
IL-4-mediated drug resistance in colon cancer stem cells
2008
Cancer stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Cancer stem cells are thus likely to be responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The CD133 glycoprotein was recently described as a reliable cancer stem-like cell marker in colon carcinoma. CD133+ cells are both necessary and sufficient to initiate tumour growth in animal models. The CD133+ cell population and spheroid cultures contain cells expressing the stem cell marker Musashi-1 which is involved in maintenance of stem cell fate in several tissues and importantly, this expression is maintained in stem-like cells…
Male fertility in long-term survivors of childhood ALL.
1999
A study of fertility was conducted in postpubertal male patients who had been treated for acute lymphoblastic leukemia (ALL) during childhood or adolescence between 1970 and 1980. Thirteen men (age 18 to 35 years) participated on a volunteer basis. Their age at diagnosis was between 2 and 15 years. Therapy followed the protocol ''Memphis VII (Pinkel)." Interview, physical examination, andrological studies (ejaculate), and hormone status (luteinizing hormone, follicle-stimulating hormone, and testosterone) were performed at least 5 years after completion of therapy. No normozoospermia was achieved; 10 patients were identified with asthenozoospermia and 3 patients with azoospermia. With respe…
Endometrial receptivity and implantation are not affected by the presence of uterine intramural leiomyomas: a clinical and functional genomics analys…
2008
Uterine leiomyomas are the most frequent benign tumors during reproductive age. Whether intramural leiomyomas cause infertility and should be removed is controversial because no study has addressed the underlying mechanism of infertility.The objective of the study was to test the effect of intramural leiomyomas on endometrial function by comparing gene during the window of implantation and implantation in an oocyte donation program, in which the quality of the embryos replaced is similar and the endocrine environment of the endometrium is standardized by exogenous steroids.Human endometria of women with single intramural leiomyomas (group A,5 cm and group B,or =5 cm) and controls (group C) …
The effect of cancer treatment on female fertility and strategies for preserving fertility.
2006
Aggressive chemotherapy and radiotherapy in young patients with cancer has greatly enhanced the life expectancy of these patients, but these treatments often cause infertility because of the massive destruction of the ovarian reserve resulting in premature ovarian failure (POF). This review focuses on the effect of cancer treatments on fertility and on the various surgical and assisted-reproduction innovations that are available to provide the patient with the option of future pregnancies. As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better inte…