Search results for "Combretastatin"

Abstract C097: Pyrrolo[2′,3′:3,4]cyclohepta[1,2-d][1,2]oxazoles: A new class of antimitotic agents

2019

Abstract Tubulin-binding molecules constitute an important class of antineoplastic agents, with broad activity in both solid and hematologic malignancies. Oxazoles represent the core structure of many drug candidates with multiple targets, providing an attractive scaffold in medicinal chemistry. Diaryl[1,2]oxazoles have emerged as potent analogues of the antitubulin compound combretastatin A-4 (CA-4). Naphtylcombretastin and its derivatives incorporating the isoxazole moiety displayed potent cytotoxic effects and inhibition of tubulin polymerization. In particular, 5-(naphthalen-2-yl)-4-(TMP)-1,2-oxazole and 4-(naphthalen-2-yl)-5-(TMP)-1,2-oxazole showed the same inhibitory potency as napht…

Isoxazolo[5,4-e]isoindole a new ring system with potent antitumor activity

2011

Molecular Classification of 5-Amino-2-Aroylquinolines and 4-Aroyl-6,7,8-Trimethoxyquinolines as Highly Potent Tubulin Polymerization Inhibitors

2013

Algorithms for classification and taxonomy are proposed based on criteria as information entropy and its production. It is classified a series of 5-amino-2-aroylquinolines (AAQs) and 4-aroyl-6,7,8-trimethoxyquinolines (TMQs) combretastatin analogues for anti-cancer activity. 5-Amino-6-methoxy-2-aroylquinoline AAQ showed anti-proliferative activity more potent as compared to combretastatin A-4 (CA4), against various human cancer cell lines and a multidrug resistance (MDR) cancer cell line. On the basis of AAQ/TMQ structure–activity relationship new derivatives are designed. The AAQs/TMQs are classified using nine characteristic chemical properties in molecules. Many classification algorithms…

4-(3-Hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione

2005

The title compound, C20H19NO7, crystallizes in the space group Pna21. X-ray analysis shows the compound has the desired 3′-hydroxy and 4′-methoxy substitution pattern, as in the natural template combretastatin A-4.

Synthesis of N-acyl Derivatives of Aminocombretastatin A-4 and Study of their Interaction with Tubulin and Downregulation of c-Myc.

2021

11 p.-9 fig.-4 tab.

Heterocyclic and Phenyl Double-Bond-Locked Combretastatin Analogues Possessing Potent Apoptosis-inducing activity in HL60 and in MDR Cell lines

2005

Two new series of combretastatin (CA-4) analogues have been prepared. The alkenyl motif of CA-4 was replaced either by a five-membered heterocyclic (isoxazoline or isoxazole) or by a six-membered ring (pyridine or benzene). The new compounds have been evaluated for their effects on tubulin assembly and for cytotoxic and apoptotic activities. Five compounds (18b, 20a, 21a, 34b, and 35b) demonstrated an attractive profile of cytotoxicity (IC501 microM) and apoptosis-inducing activity but poor antitubulin activity. The isoxazoline derivatives 18b, 20a, and 21a, demonstrated potent apoptotic activity different from that of natural CA-4. Their ability to block most cells in the G2 phase suggests…

Design, Synthesis, and Biological Evaluation of 3,4-Diarylmaleimides as Angiogenesis Inhibitors

2006

The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 microM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely related to this lead, no other compound was found to be active in the tubulin polymerization assay. However, by screening in the in vivo chick embryo assay 10 was identified as a potent angiogenesis inhibitor indicating an alternative target. Indeed, molecular modeling studies suggest a reasonable binding mode of 10 at the ATP-binding site of the model kinase CDK2. Motivated by these results, analogues of 10 were screened for inhibitory activity in…

Structural determinants of resveratrol for cell proliferation inhibition potency: experimental and docking studies of new analogs.

2010

International audience; Resveratrol is the subject of intense research because of the abundance of this compound in the human diet and as one of the most valuable natural chemopreventive agents. Further advances require new resveratrol analogs be used to identify the structural determinants of resveratrol for the inhibition potency of cell proliferation by comparing experimental and docking studies. Therefore, we synthesized new trans/(E)- and cis/(Z)-resveratrol - analogs not reported to date - by modifying the hydroxylation pattern of resveratrol and a double bond geometry. We included them in a larger panel of 14 molecules, including (Z)-3,5,4'-trimethoxystilbene, the most powerful molec…

Synthesis and Biological Evaluation of Combretastatin A-4 and Three Combretastatin-Based Hybrids

2012

The syntheses of combretastatin A-4 from gallic acid and of three combretastatin-based hybrids are described. Starting from commercial gallic acid, the phosphonium salt (3,4,5-trimethoxybenzylphosphonium bromide) is synthesized and coupled, through a Wittig reaction, with several aldehydes, including methoxymethyl-protected isovanillin, the aldehyde γ-bicyclohomofarnesal having a labdane skeleton, 3-(3-pyridyl) propanal, and furfural. The biological properties of the cis-coupled compounds as cytotoxic, antiviral and antifungal agents are also reported. In addition, pyrogallol, gallic and 3,4,5-trimethoxybenzoic acids have been studied biologically.

Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements

2018

Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured. The tricyclic compounds show antiproliferative activity similar to that of combretastatin A-4, even though they are not so active in arresting the cell cycle. However, some diolefin precursors are able to cause accumulation of ce…