Structure–activity relationships of indole compounds derived from combretastatin A4: Synthesis and biological screening of 5-phenylpyrrolo[3,4- a]carbazole-1,3-diones as potential antivascular agents

• Published in: European journal of medicinal chemistry Vol. 45; no. 9; pp. 3726 - 3739
• Main Authors: Ty, Nancy, Dupeyre, Grégory, Chabot, Guy G., Seguin, Johanne, Quentin, Lionel, Chiaroni, Angèle, Tillequin, François, Scherman, Daniel, Michel, Sylvie, Cachet, Xavier
• Format: Journal Article
• Language: English
• Published: PARIS Elsevier Masson SAS 01.09.2010; Elsevier
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Biological and medical sciences; Blood Vessels - drug effects; Carbazoles - chemical synthesis; Carbazoles - chemistry; Carbazoles - pharmacology; Cell Line, Tumor; Chemical Sciences; Chemistry, Medicinal; Drug Evaluation, Preclinical; Endothelial cells; General aspects; Humans; Life Sciences & Biomedicine; Medical sciences; Mice; Multicomponent reactions; Organic chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Protein Multimerization - drug effects; Protein Structure, Quaternary; Science & Technology; Stilbenes - chemistry; Structure-Activity Relationship; Tubulin; Tubulin - chemistry; Tubulin - metabolism; Vascular-disrupting agents; Antitumor agents; Multicomponent reactions; Tubulin; Vascular-disrupting agents; Endothelial cells; VASCULAR DISRUPTING AGENTS; A-4 ANALOGS; TUBULIN POLYMERIZATION; ANTINEOPLASTIC AGENTS; CELL-GROWTH; SU5416; THERAPY; 3-AROYLINDOLES; CONFORMATIONALLY RESTRICTED ANALOGS; INHIBITORS; Antineoplastic agent; Endothelial cell; Spontaneous; Cytotoxicity; Antivascular agent; Vascularization; Structure activity relation; B16-Melanoma; Chemical synthesis; Antimitotic; Tumor cell; Multicomponent reaction; Rodentia; Antitubulin; Malignant tumor; In vitro; Stilbene derivatives; Screening; Vertebrata; Mammalia; Mouse; Animal; Cancer

A series of 5-(3′,4′,5′-trimethoxyphenyl)pyrrolo[3,4- a]carbazole-1,3(2 H,10 H)-diones was designed as cis-restricted analogues of 3-aroylindoles, arylthioindoles and 3-benzylidoneindolin-2-ones derived from combretastatin A4 (CA-4). Starting from various indoles, compounds were synthesized by means...