Synthesis and biological evaluation of pyrimidine bridged combretastatin derivatives as potential anticancer agents and mechanistic studies

Kumar, Bhupinder; Sharma, Praveen; Gupta, Vivek Prakash; Khullar, Madhu; Singh, Sandeep; Dogra, Neeti; Kumar, Vinod

doi:10.1016/j.bioorg.2018.02.027

Cited by 74 publications

(30 citation statements)

References 36 publications

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“…It is also stated that the compounds do not have DPPH radical scavenging properties. According to the results of the study, it has been showed that the compounds can disrupt the cellular antioxidant defense system and trigger the apoptotic pathway by causing increased ROS in the cell [28].…”

Section: Antioxidant Activitymentioning

confidence: 99%

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

et al. 2020

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Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.

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Section: Antioxidant Activitymentioning

confidence: 99%

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

et al. 2020

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“…In this regard, the studies about potential anticancer from the organic compounds as anticancer agent and drugs are extensively investigated by many researchers. [25,26] Recently, formazan derivatives and their conjugates showed variant promising anticancer activity in photodynamic therapy (PDT) activity against cancer cells. [27] As well, the formazans are comparatively more practical in the recognition of efficiency of anti-cancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Substituent‐Dependent Absorption Spectra, Electrochemical and Antiproliferative Activity Studies of Some 3‐(4‐(Benzyloxy)phenyl)‐5‐(4‐methoxyphenyl)‐1‐(substitutedphenyl)formazans

Turkoglu

Akkoç

2020

ChemistrySelect

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We have reported the effect of electron donating and withdrawing substituents on absorption and electrochemical properties of formazan derivatives as well as antiproliferative activity. New formazans F2 and F4 bearing electron donating subunits have been synthesized, and characterized via elemental analysis and various spectroscopic techniques. The substituent effects and solvatochromic of formazan derivatives F2-F5 having different substituents on 1-phenyl ring in eleven solvents were investigated by absorption spectroscopy. Whilst their absorption bands are only slightly dependent on the polarities of solvents, the considerable alteration was detected by modifying the electronic characteristic and positions of the substituents. Then, the antiproliferative activity of all compounds was investigated in four cancer cell lines using MTT and XTT assay methods. The IC 50 values of F2 and F4, having electron donating methoxy and methyl subunits were obtained in the ranges of 10.60 and 21.53 μM in DLD-1 and HepG2 cell lines. Our study demonstrates that F2 and F4 are more active than the positive control drug used.

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“…Ring B appears to be responsible for the irreversible nature of colchicine binding to tubulin, although it may also contribute to its toxic effects [ 11 , 17 ]. Therefore, currently much interest has focused on structural modification of 1 in the hope of improving its anticancer activity [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives

Majcher

Klejborowska

Moshari

et al. 2018

Cells

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Microtubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells.

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Synthesis and biological evaluation of pyrimidine bridged combretastatin derivatives as potential anticancer agents and mechanistic studies

Cited by 74 publications

References 36 publications

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

Substituent‐Dependent Absorption Spectra, Electrochemical and Antiproliferative Activity Studies of Some 3‐(4‐(Benzyloxy)phenyl)‐5‐(4‐methoxyphenyl)‐1‐(substitutedphenyl)formazans

Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives

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