Molecules, Vol. 24, Pages 2656: Structural and Biological Investigations for a Series of N-5 Substituted Pyrrolo3,2-dpyrimidines as Potential Anti-Cancer Therapeutics

Molecules, Vol. 24, Pages 2656: Structural and Biological Investigations for a Series of N-5 Substituted Pyrrolo[3,2-d]pyrimidines as Potential Anti-Cancer Therapeutics Molecules doi: 10.3390/molecules24142656 Authors: Brian M. Cawrse Nia’mani M. Robinson Nina C. Lee Gerald M. Wilson Katherine L. Seley-Radtke Pyrrolo[3,2-d]pyrimidines have been studied for many years as potential lead compounds for the development of antiproliferative agents. Much of the focus has been on modifications to the pyrimidine ring, with enzymatic recognition often modulated by C2 and C4 substituents. In contrast, this work focuses on the N5 of the pyrrole ring by means of a series of novel N5-substituted pyrrolo[3,2-d]pyrimidines. The compounds were screened against the NCI-60 Human Tumor Cell Line panel, and the results were analyzed using the COMPARE algorithm to elucidate potential mechanisms of action. COMPARE analysis returned strong correlation to known DNA alkylators and groove binders, corroborating the hypothesis that these pyrrolo[3,2-d]pyrimidines act as DNA or RNA alkylators. In addition, N5 substitution reduced the EC50 against CCRF-CEM leukemia cells by up to 7-fold, indicating that this position is of interest in the development of antiproliferative lead compounds based on the pyrrolo[3,2-d]pyrimidine scaffold.
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research

Related Links:

Conditions:   Acute Myeloid Leukemia;   Myelodysplastic Syndromes;   Myeloproliferative Neoplasm;   Aplastic Anemia Intervention:   Sponsor:   National Taiwan University Hospital Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
(Natural News) The popularity of avocados has risen in recent years – not only because they are delicious, but because they are highly nutritious superfoods. One of the many health benefits they offer is their ability to ward off cancer. Avocados contain avocatin B, which is a compound found to fight against a type of...
Source: NaturalNews.com - Category: Consumer Health News Source Type: news
ConclusionThe findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.
Source: Journal of Ginseng Research - Category: Complementary Medicine Source Type: research
Publication date: Available online 7 August 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Deepu Madduri, Madhav V. Dhodapkar, Sagar Lonial, Sundar Jagannath, Hearn Jay ChoAbstractTherapeutic monoclonal antibodies targeting SLAMF7 and CD38 are the first classes of targeted immunotherapies approved for multiple myeloma, a cancer of plasma cells. These agents are effective, particularly in combination with the immunomodulatory drugs lenalidomide and pomalidomide. The next generation of myeloma immunotherapy under investigation consists of T-cell–directed strategies designed to promote cytotoxic activity a...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Acute leukemias are a heterogeneous group of aggressive malignant neoplasms associated with severe morbidities due to the nonselectivity of current chemotherapeutic drugs to nonmalignant cells. The investigation of novel natural and synthetic structures that might be used for the development of new drugs with greater efficiency and selectivity to leukemic cells is mandatory. In this context, thiosemicarbazones have been well described in the literature by their several biological properties and their reaction is known as versatile, low-cost, and highly chemoselective. With this perspective, this study aimed to investigate ...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Papers Source Type: research
Synergistic Effects of PI3K and c-Myc Co-targeting in Acute Leukemia: Shedding New Light on Resistance to Selective PI3K-δ Inhibitor CAL-101. Cancer Invest. 2019 Aug 14;:1-14 Authors: Riyahi N, Safaroghli-Azar A, Sheikh-Zeineddini N, Sayyadi M, Bashash D Abstract Enthusiasms into the application of PI3K-δ inhibitor CAL-101 has been muted due to the over-activation of compensatory molecules. Our results delineated that c-Myc suppression using 10058-F4 enhanced CAL-101 cytotoxicity in less sensitive cells through different mechanisms based on p53 status; while CAL-101-plus-10058-F4 induced G1...
Source: Cancer Investigation - Category: Cancer & Oncology Tags: Cancer Invest Source Type: research
In the original publication of this article [1], there is a mistake in Fig. 4E.
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Correction Source Type: research
While aberrant protein glycosylation is a recognised characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumourigenesis. This glycomics ‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of humanN‐glycosylation [Man1 ‐3GlcNAc2Fuc0 ‐1], and human cancers. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non ‐cancerous specimens were profiled from 467 published and unpublished PGC‐LC‐MS/MSN‐glycome datasets collecte...
Source: Proteomics - Category: Biochemistry Authors: Tags: Research Article Source Type: research
rner Niels Schaft Chimeric antigen receptor (CAR)-T cells already showed impressive clinical regressions in leukemia and lymphoma. However, the development of CAR-T cells against solid tumors lags behind. Here we present the clinical-scale production of CAR-T cells for the treatment of melanoma under full GMP compliance. In this approach a CAR, specific for chondroitin sulfate proteoglycan 4 (CSPG4) is intentionally transiently expressed by mRNA electroporation for safety reasons. The clinical-scale protocol was optimized for: (i) expansion of T cells, (ii) electroporation efficiency, (iii) viability, (iv) cryopreser...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Technical Note Source Type: research
This study identified HOXA3-10 genes as potential AML therapeutic targets and prognostic markers.
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
More News: Cancer | Cancer & Oncology | Chemistry | Leukemia