Dataset Information

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

ABSTRACT: Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic kinesin Eg5. Heterocyclic-fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the in vitro antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized via Biginelli multicomponent condensation of fatty ?-ketoester in good yields using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Following synthesis, their in vitro antitumoral activities were investigated. Notably, all analogues tested were active against rat glioblastoma cells. Superior activity was observed by analogues derived from palmitic and stearic fatty acid chains; these compounds were the most potent molecules, showing 13-fold higher potency than monastrol with IC₅₀ values of 5.11 and 6.85 ?M, respectively. These compounds could provide promising new lead derivatives for more potent antitumor drugs.

SUBMITTER: De Oliveira FS

PROVIDER: S-EPMC6096354 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

De Oliveira Franciele S FS De Oliveira Patrick M PM Farias Luana M LM Brinkerhoff Rafael C RC Sobrinho Rui Carlos M A RCMA Treptow Tamara M TM Montes D'Oca Caroline R CR Marinho Marcelo A G MAG Hort Mariana A MA Horn Ana P AP Russowsky Dennis D Montes D'Oca Marcelo G MG

MedChemComm 20180530 8

Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic kinesin Eg5. Heterocyclic-fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the <i>in vitro</i> antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized <i>via</i> Biginelli multic ...[more]

PMID: 30151081

Similar Datasets

Project description:Breast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC50 of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC50 = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC50 = 0.093 µM) compared to Sorafenib (IC50 = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.

Dataset Information

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

Publications

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets