Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation

Kaffy, Julia; Pontikis, Renée; Carrez, Danièle; Croisy, Alain; Monneret, Claude; Florent, Jean‐Claude

doi:10.1016/j.bmc.2006.02.001

Cited by 132 publications

(74 citation statements)

References 42 publications

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“…Combrestatin analogues having five membered heterocycles (isoxazole, isoxazoline, oxadiazole) were synthesized and evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. The compound 55 showed good antitubulin activity at 1.2 µM [66]. Isoxazoline was synthesized and tested for antimicrobial activity against Staphylococcus aureus, Bacillus megaterium, Aspergillus niger and Asterophora parasitica and compound 56 has shown good activity against all strains with 18-22 mm zone of inhibition [67].…”

Section: Analogues Of Chalcones Pyrazoline Analogues With Various Phamentioning

confidence: 99%

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Sapra¹,

Sharma²

2016

Chem Sci J

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Although chalcones symbolize an important pharmacophore for variety of biological actions, however their analogues are also reported to be equally important for plethora of biological actions. In the present review, a comprehensive study of chalcones derived molecules (like pyrazoles, isoxazoles, pyridine, pyrimidine) their pharmacological actions, mechanism of action, structure activity relationship studies have been described. which includes anti-proliferative, anti-inflammatory, antioxidant, proapoptotic, anti-bacterial and anti-adhesive effects [18]. Analogues of chalcones Pyrazoline analogues with various pharmacological activities:Pyrazole nucleus present in compounds exhibit wide range of biological activity. Introduction of a pyrazole ring in the chalcones between the two aryl rings increase the cytotoxic activity against a series of human cancer cell lines. Dhar et al. [19] synthesized a series of 1-acetyl-3,5-diaryl-4,5-dihydro-(H)-pyrazoles and assayed for in vitro cytotoxicity against PC-3, OVCAR, IMR-32, HEP-2 human cancer cell lines, compound 1 showed broad spectrum cytotoxic activity against all the four cell lines. The activity shown by the compounds conclude that (i) Substitution on phenyl ring showed marked effect on cytotoxic activity, (ii) Presence of electron donating groups on phenyl ring led to enhanced activity whereas electron withdrawing group except NO 2 reduces the cytotoxic activity, (iii) Replacement of phenyl ring with heterocyclic ring also reduces the cytotoxic potential and napthyl ring on both sides are more beneficial for cytotoxic potential Chemical Sciences JournalChem ic a l S cience s J o u rnal

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Section: Analogues Of Chalcones Pyrazoline Analogues With Various Phamentioning

confidence: 99%

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Sapra¹,

Sharma²

2016

Chem Sci J

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“…Stability issues were addressed by extensive alkene substitutions to a conformationally restricted structure: many in the form of heterocyclic groups (rings containing elements other than carbon) (Rajak et al, 2013;Lipeeva et al, 2014;Galli et al, 2015). Examples of alkene modifications include the following: imidazoles, furanones, thiazoles, pyrazoles, indoles, isoxazoles, and b-lactams (Medarde et al, 1999;Kaffy et al, 2006;O'Boyle et al, 2010;Banimustafa et al, 2013;Lin et al, 2013;Tsyganov et al, 2013;Mahal et al, 2015). To date, no cis-restricted synthetic analogs have progressed to clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Combretastatins: More Than Just Vascular Targeting Agents?

Greene

Meegan

Zisterer

2015

J Pharmacol Exp Ther

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Several prodrugs of the naturally occurring combretastatins have undergone extensive clinical evaluation as vascular targeting agents (VTAs). Their increased selectivity toward endothelial cells together with their innate ability to rapidly induce vascular shutdown and inhibit tumor growth at doses up to 10-fold less than the maximum tolerated dose led to the clinical evaluation of combretastatins as VTAs. Tubulin is well established as the molecular target of the combretastatins and the vast majority of its synthetic derivatives. Furthermore, tubulin is a highly validated molecular target of many direct anticancer agents routinely used as front-line chemotherapeutics. The unique vascular targeting properties of the combretastatins have somewhat overshadowed their development as direct anticancer agents and the delineation of the various cell death pathways and anticancer properties associated with such chemotherapeutics. Moreover, the ongoing clinical trial of OXi4503 (combretastatin-A1 diphosphate) together with preliminary preclinical evaluation for the treatment of refractory acute myelogenous leukemia has successfully highlighted both the indirect and direct anticancer properties of combretastatins. In this review, we discuss the development of the combretastatins from nature to the clinic. The various mechanisms underlying combretastatin-induced cell cycle arrest, mitotic catastrophe, cell death, and survival are also reviewed in an attempt to further enhance the clinical prospects of this unique class of VTAs.

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“…Generally, introduction of N-containing 5-membered heterocycles as linkers between two aryl rings in CA4 analogues (Figure 1, III) resulted in potent cytotoxic compounds with antimitotic microtubule destabilizing mode of action. [11][12][13][14][15][16][17][18][19][20] Similarly, CA4 analogues with bicyclic triazolopyrimidine linker, halogen substituted triazolopyrimidines (Figure 1, IV), displayed cytotoxicity against human cancer cell lines with IC50 in nanomolar concentration range. 21 In the present study, polymethoxyhydroxy-substituted diaryltriazolopyrimidines 9 were found to be inactive up to 4 microMol concentration.…”

Section: Page 158mentioning

confidence: 99%

“…Spontaneous isomerization to the trans-double bond observed both in vitro and in vivo causes a dramatic decrease of biological activity. 10 To stabilize the active cis-conformation, several heteroaromatic rings, such as pyrazole, 11 imidazole, 11,12 thiazole, 11 isoxazole, 13,14 1,2,3-thiadiazole, 15 isomeric triazoles, 11,16,17 and tetrazole 11,[18][19][20] have been introduced as a nonisomerizable and metabolically stable isosteric equivalent of cis-double bond (Figure 1, III), resulting in highly active microtubule destabilizing antimitotic agents. Replacement of the double bond by triazolopyrimidine yielded diaryl-o-substituted-triazolopyrimidines (Figure 1, IV) with pronounced cytotoxicity against human cancer cells both in vitro and in mouse xenograft model.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antimitotic properties of ortho-substituted polymethoxydiarylazolopyrimidines

Chernyshova¹,

Tsyganov²,

Khrustalev³

et al. 2017

Arkivoc

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Ortho-substituted polymethoxydiarylazolopyrimidines were synthesized using polymethoxysubstituted benzaldehydes and acetophenones as starting material. X-ray crystallography data clearly confirmed that the subsequent cyclization of 3-amino-1,2,4-triazole with ketoaldehydes yielded polymethoxyphenylsubstituted 6,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines as single isomers. All compounds were evaluated in vivo using phenotypic sea urchin embryo assay. 6-(4-Methoxyphenyl)-7-(3,4,5-trimethoxyphenyl)pyrazolo [1,5-a]pyrimidine showed antimitotic microtubule destabilizing activity. The importance of aryl rings substituents in diaryltriazolopyrimidines for their antiproliferative antitubulin effect has been suggested.

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Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation

Cited by 132 publications

References 42 publications

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Combretastatins: More Than Just Vascular Targeting Agents?

Synthesis and antimitotic properties of ortho-substituted polymethoxydiarylazolopyrimidines

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