Antiproliferative Activity of (−)‐Isopulegol‐based 1,3‐Oxazine, 1,3‐Thiazine and 2,4‐Diaminopyrimidine Derivatives

Abstract

A series of novel heterocyclic structures, namely 1,3‐oxazines, 1,3‐thiazines and 2,4‐diaminopyrimidines, were designed and synthesised. The bioassay tests demonstrated that, among these analogues, 2,4‐diaminopyridine derivatives showed significant antiproliferative activity against different human cancer cell lines (A2780, SiHa, HeLa, MCF‐7 and MDA‐MB‐231). Pyrimidines substituted with N 2 ‐( p ‐trifluoromethyl)aniline, in particular, displayed a potent inhibitory effect on the growth of cancer cells. Structure–activity relationships were also studied from the aspects of stereochemistry on the aminodiol moiety as well as exploring the effects of substituents on the pyrimidine scaffold.

Stereoselective Synthesis and Antiproliferative Activities of Tetrafunctional Diterpene Steviol Derivatives

“…However, the utilised cancer panel detected no substantial cell line selective action. In addition, some compounds (11)(12)(13)(14) exhibited more pronounced antiproliferative activity than the reference agent cisplatin, and non-cancerous fibroblast cells were damaged in the same concentration range, indicating a general cytotoxic property of the tested substances.…”

“…3.3.7. (4R,4aS,6aR,7R,8R,11aS,11bS)-Methyl 8-((((R)-1-(4-Fluorophenyl)ethyl)amino)methyl)-7,8,9-trihydroxy-4,11bdimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate (11) The reaction was accomplished with (R)-4-fluoro-α-methylbenzylamine, as described in the general procedure. Yield: 68 mg (50%); white crystals; m.p.…”

“…For example, pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties [ 7 ], whereas the immunosuppressant antibiotic myriocin [ 8 , 9 ] and penaresdin A and B were identified as potent actomyosin ATP-ase activators [ 10 ]. A large majority of these compounds are derived from commercially available monoterpenes, such as (–)-isopulegol, α- or β-pinene [ 6 , 11 ], while only a handful of chiral sources of diterpenes are commercially available in a large scale [ 12 , 13 , 14 ]. Among them, stevioside ( I ) is a frequently used source of bioactive diterpenoid derivatives since it can be isolated at an industrial scale from Stevia rebaudiana and it can be easily transformed to its aglycons, steviol and isosteviol [ 15 , 16 , 17 , 18 ].…”

Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohol regioisomers

“…2,4-Diaminopyrimidine derivatives with potent antiproliferative activity were prepared starting from pinaneand (−)-isopulegol-based 1,3-aminoalcohols. 20,21 In our previous work, we designed and evaluated the antiproliferative activity of a series of N-substituted allo-gibberic acid-based aminodiols. We found that N-naphthylethyl-substituted aminodiol derivatives showed the most promising antiproliferative activity.…”

“…2,4-Diaminopyrimidine derivatives with potent antiproliferative activity were prepared starting from pinane- and (−)-isopulegol-based 1,3-aminoalcohols. 20,21…”