Synthesis and antitumor activity of tropolone derivatives. 2

Abstract

Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha-disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4.

Plant Troponoids: Chemistry, Biological Activity, and Biosynthesis

“…As shown in previous section, some natural troponoids and synthetic derivatives showed strong inhibitory effects on ribonucleotide reductase activity in virus and cancer cells [42][43][44][45][46][47][48][49][50]. These activities might be used in cancer therapy and as antiviral medicines.…”

“…Some pro-troponoids and synthesized troponoids with interesting bioactivity. many of which can block the cellular ribonucleotide reductase and are of great interest as inhibitors of human immunodeficiency virus (HIV)-type 1 replication [42][43][44][45][46][47][48][49][50] or in cancer chemotherapy. All of these antitumor activities are related to ion chelation in the active site of ribonucleotide reductase.…”

1-(4-Chlorophenyl)-6,7-dimethoxyisochroman

“…These are also intermediates in the synthesis of pharmaceuticals and drugs. 1-Aryl-6,7-dimethoxyisochromans are an important class of isochromans which exhibit a wide range of biological activities such as analgesic, muscle relaxant, antidepressant, anti-inflammatory, antihistaminic, anticoagulant and antihypertensive (Dobson et al, 1975;Yamato et al, 1985;McCall et al, 1982). 6,7-Dimethoxyisochromans substituted at C-1 via a one-to three-carbon chain with arylpiperazines, p-fluorophenyl, etc., are hypotensives which lower blood pressure, presumably by both peripheral and central -adrenoreceptor blockade (TenBrink et al, 1996).…”

6,7-Dimethoxy-1-(4-methoxyphenyl)isochroman

“…Isochroman derivatives also exhibit plant-growth regulatory and herbicidal activities (Bianchi et al, 2004;Cutler et al, 1997), they are oestrogen receptors (Liu et al, 2005), dopamine receptor ligands (TenBrink et al, 1996), and fragrances, such as galaxolide (Frá ter et al, 1999). 1-Aryl-6,7-dimethoxyisochromans have shown a wide range of biological activities such as analgesic, muscle relaxant, antidepressant, antiinflammatory, antihistaminic and anticoagulant, hypotensive with peripheral and central activities and are adrenergic antagonists (Dobson & Humber 1975;Yamato et al, 1985;McCall et al, 1982). The oxa-Pictet-Spengler reaction is a variation of the Pictet-Spengler reaction in which a phenethyl alcohol reacts with a carbonyl compound to give a 1-substitued isochroman derivative (Guiso et al, 2001).…”