bpr0l075 and fosbretabulin

bpr0l075 has been researched along with fosbretabulin* in 2 studies

Other Studies

2 other study(ies) available for bpr0l075 and fosbretabulin

Article	Year
Potent antitubulin tumor cell cytotoxins based on 3-aroyl indazoles. Journal of medicinal chemistry, 2007, Mar-08, Volume: 50, Issue:5 A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [3H]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site. Topics: Acetylene; Animals; Binding Sites; Binding, Competitive; Cattle; Cell Line, Tumor; Colchicine; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indazoles; Radioligand Assay; Stilbenes; Structure-Activity Relationship; Tubulin; Tubulin Modulators	2007
Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents. Journal of medicinal chemistry, 2004, Aug-12, Volume: 47, Issue:17 The synthesis and study of the structure-activity relationships of two new classes of synthetic antitubulin compounds based on 1-aroylindole and 3-aroylindole skeletons are described. Lead compounds 3, 10, and 14 displayed potent cytotoxicities with IC50 = 0.9-26 nM against human NUGC3 stomach, MKN45 stomach, MESSA uterine, A549 lung, and MCF-7 breast carcinoma cell lines. The inhibition of proliferation correlated with in vitro polymerization inhibitory activities. Structure-activity relationships revealed that 6-methoxy substitution of 3-aroylindoles and 5-methoxy substitution of 1-aroylindoles contribute to a significant extent for maximal activity by mimicking the para substitution of the methoxy group to the carbonyl group in the case of aminobenzophenones. Addition of a methyl group at the C-2 position on the indole ring exerts an increased potency. The 3,4,5-trimethoxybenzoyl moiety was necessary for better activity but not essential and can be replaced by 3,5-dimethoxybenzoyl and 3,4,5-trimethoxybenzyl moieties. We conclude that 1- and 3-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment. Topics: Antineoplastic Agents; Biopolymers; Cell Line, Tumor; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Indoles; Molecular Structure; Stilbenes; Structure-Activity Relationship; Tubulin; Tubulin Modulators	2004

Article

Year

Potent antitubulin tumor cell cytotoxins based on 3-aroyl indazoles.

Journal of medicinal chemistry, 2007, Mar-08, Volume: 50, Issue:5

A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [3H]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site.

Topics: Acetylene; Animals; Binding Sites; Binding, Competitive; Cattle; Cell Line, Tumor; Colchicine; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indazoles; Radioligand Assay; Stilbenes; Structure-Activity Relationship; Tubulin; Tubulin Modulators

2007

Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents.

Journal of medicinal chemistry, 2004, Aug-12, Volume: 47, Issue:17

The synthesis and study of the structure-activity relationships of two new classes of synthetic antitubulin compounds based on 1-aroylindole and 3-aroylindole skeletons are described. Lead compounds 3, 10, and 14 displayed potent cytotoxicities with IC50 = 0.9-26 nM against human NUGC3 stomach, MKN45 stomach, MESSA uterine, A549 lung, and MCF-7 breast carcinoma cell lines. The inhibition of proliferation correlated with in vitro polymerization inhibitory activities. Structure-activity relationships revealed that 6-methoxy substitution of 3-aroylindoles and 5-methoxy substitution of 1-aroylindoles contribute to a significant extent for maximal activity by mimicking the para substitution of the methoxy group to the carbonyl group in the case of aminobenzophenones. Addition of a methyl group at the C-2 position on the indole ring exerts an increased potency. The 3,4,5-trimethoxybenzoyl moiety was necessary for better activity but not essential and can be replaced by 3,5-dimethoxybenzoyl and 3,4,5-trimethoxybenzyl moieties. We conclude that 1- and 3-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.

Topics: Antineoplastic Agents; Biopolymers; Cell Line, Tumor; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Indoles; Molecular Structure; Stilbenes; Structure-Activity Relationship; Tubulin; Tubulin Modulators

2004