Dataset Information

Betulinic Acid-Nitrogen Heterocyclic Derivatives: Design, Synthesis, and Antitumor Evaluation in Vitro.

ABSTRACT: Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21 BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) assay. The majority of these derivatives showed much stronger cytotoxic activity than BA. Remarkably, the most potent compound 7e (the half maximal inhibitory concentration (IC50) of which was 2.05 ± 0.66 ?M) was 12-fold more toxic in vitro than BA-treated Hela. Furthermore, multiple fluorescent staining techniques and flow cytometry collectively revealed that compound 7e could induce the early apoptosis of Hela cells. Structure-activity relationships were also briefly discussed. The present study highlighted the importance of introducing nitrogen heterocyclic rings into betulinic acid in the discovery and development of novel antitumor agents.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7070564 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Betulinic Acid-Nitrogen Heterocyclic Derivatives: Design, Synthesis, and Antitumor Evaluation in Vitro.

Yang Yuqin Y Xie Tianxin T Tian Xuehao X Han Nana N Liu Xiaojing X Chen Hongshan H Qi Jinchai J Gao Feng F Li Wen W Wu Qianwen Q Huo Su S Gu Yuhao Y Dai Ziqi Z Wang Penglong P Lei Haimin H

Molecules (Basel, Switzerland) 20200220 4

Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21 BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) ...[more]

PMID: 32093264

Similar Datasets

Project description:Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde (1) with Curcumin (2) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5H-furo [3, 2-g] chromen-5-one derivatives 4a?d, 6a?d, 7, 8a?d, 9 and 10 were synthesized by the reactions of furochromone carbaldehyde (1) with different reagents (namely: appropriate amine 3a?d, appropriate hydrazine 5a?d, hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate). The structure of the synthesized products had been confirmed from their spectroscopic data (IR, ¹H-NMR, 13C-NMR and mass spectra). In the present investigation, the newly synthesized products were screened using the MTT colorimetric assay for their in vitro inhibition capacity in two human cancer cell lines (hepatocellular carcinoma (HEPG2) and breast cancer (MCF-7) as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-flurouracil and doxorubicin. The anticancer activity results indicated that the synthesized products 4c and 8b showed growth inhibition activity against HEPG2 cell line and synthesized products 4b and 8a showed growth inhibition activity against MCF-7, but with varying intensities in comparison to the known anticancer drugs, 5-flurouracil and doxorubicin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. The molecular docking study revealed that compounds 4b, 8a and 8b were the most effective compounds in inhibiting CDk2, and, this result was in agreement with cytotoxicity assay.

Dataset Information

Betulinic Acid-Nitrogen Heterocyclic Derivatives: Design, Synthesis, and Antitumor Evaluation in Vitro.

Publications

Betulinic Acid-Nitrogen Heterocyclic Derivatives: Design, Synthesis, and Antitumor Evaluation <i>in Vitro</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure