Novel isatin derivatives of podophyllotoxin: synthesis and cytotoxic evaluation against human leukaemia cancer cells as potent anti-MDR agents

Zhang, Lei; Fan, Chun‐Lin; Wang, Jing; Chen, Yongzheng; Zhang, Zeguo; Lin, Yu-Shen; Zhu, Xiaofang

doi:10.1039/c5ra21217k

Cited by 31 publications

(26 citation statements)

References 57 publications

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“…To create more effective antitumor candidates that more affordable, hybridization of natural products or natural product-drug is one promising approach for designing lead compounds [ 27 , 28 ]. Recently, our group has described the synthesis and antiproliferative potential of the PPT conjugates [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ], and some derivatives showed dramatic activity. For example, the artesunate-podophyllotoxin conjugate exhibited notable cytotoxicity against several cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells

et al. 2017

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With the purpose of creating a multifunctional drug for gastric cancer treatment, a novel all-trans-retinoic acid (ATRA) conjugate with podophyllotoxin (PPT) was designed and synthesized, and its in vitro antiproliferative activity was evaluated against human gastric cancer cell lines using CCK-8 assay. The conjugate, P-A, exhibited significant anticancer activity against MKN-45 and BGC-823 cells with IC50 values of 0.419 ± 0.032 and 0.202 ± 0.055 μM, respectively. Moreover, P-A efficiently triggered cell cycle arrest and induced apoptosis in MKN-45 and BGC-823 cells due to modulation of cell cycle arrest- (CDK1, CDK2, CyclinA and CyclinB1) and apoptosis- (cleaved caspase-3, -8 and -9) related proteins, respectively. Further mechanism studies revealed that P-A could increase the expression levels of RARα and RARβ, and decrease the level of RARγ in MKN-45 and BGC-823 cells. Finally, P-A inhibited the ERK1/2 and AKT signaling in the above two cancer cell lines. More importantly, the underlying mechanisms of P-A were similar to those of precursor PPT but different with the other precursor ATRA. Together, the conjugate P-A was a promising candidate for the potential treatment of human gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells

et al. 2017

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“…A sequence of isatin derivatives of podophyllotoxin were synthesized by Zhang et al [97] and evaluated for their cytotoxic activity against human leukemia K562 cells and adriamycin-resistant K562/ADR cells using CCK-8 assay in vitro. Among them, the cytotoxicities exhibited by compounds 27a and 27b were found to be comparable or more effective than podophyllotoxin.…”

Section: Anticancer Activity Of 1h-indole-2 3-dione Derivativesmentioning

confidence: 99%

Indole Derivatives as Potential Anticancer Agents: A Review

Sachdeva

Mathur

Guleria

2020

J. Chil. Chem. Soc.

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Heterocyclic moiety serve as perfect framework on which pharmacophores can be effectively attached to produce novel drugs. Among various heterocyclic compounds, nitrogen-based heterocycles have been extensively investigated as they constitute the core structures of numerous biologically relevant molecules and have been found to be active against different types of cancers. Due to the versatility of indole, it has been a highly "privileged motif" for the target-based design and development of anticancer agents. Moreover, it has been used as a synthon for the preparation of large number of bioactive heterocycles and paved a way to develop effective targets. This review article presents comprehensive overview of anticancer potentiality of diversely substituted indole derivatives including 1H-indole-2,3dione and Spiro indole derivatives.

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“…The biological activity of podophyllotoxin has led to extensive structural modifications, resulting in several clinically useful compounds. Podophyllotoxin, exhibits anticancer [4][5][6][7] , antitumor and antiproliferative activity 8,9 . Podophyllotoxin and 4'-o-demethylepipodophyllotoxin which have shown inhibitory activity against numerous types of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Bioevaluation Study of Benzofuran Linked Tetralones as Antimitotic Agent

2018

Chem Sci Trans

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A series of new benzofuran linked tetralones (5a-h) have been prepared by chalcone route of Claisen-Schmidt condensation reaction in the presence of sodium hydroxide, 1-(benzofuran-6-yl)ethanone (1) reacts with substituted benzaldehyde (2a-h) followed by cyclopropanation of 1-(benzofuran-6-yl)-3-phenylprop-2-en-1-one (3a-h) with trimethylsulfoxonium iodide (TMSOI) in the presence of sodium hydride and Friedel-Craft's intramolecular cyclization reaction of benzofuran-6-yl(2-phenylcyclopropyl)methanone (4a-h) in the presence of anhyd. stannic chloride and acetic anhydride. The target molecules were characterized by spectral and elemental analysis and also screened for their antimitotic activity by onion root method. Taken together, our results indicated that among the entire synthesized analogues, the two new compounds 5e and 5f bearing electron donating methoxy group on para and 3,4,5-position of the phenyl moiety respectively exhibits even good antimitotic activity than other compounds.

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Novel isatin derivatives of podophyllotoxin: synthesis and cytotoxic evaluation against human leukaemia cancer cells as potent anti-MDR agents

Abstract: Compound8cexhibited cytotoxicity at nanomolar range; induced G2/M cell cycle arrest accompanied by apoptosis and down-regulated the levels of Pgp, MRP-1 and GST-π.

Cited by 31 publications

References 57 publications

Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells

Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells

Indole Derivatives as Potential Anticancer Agents: A Review

Synthesis and Bioevaluation Study of Benzofuran Linked Tetralones as Antimitotic Agent

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