SHetA2 – A Mini Review of a Promising Anticancer Drug

Heteroarotinoids (Hets) are a novel class of heterocycles which contain an aryl ring and a heterocylic ring and which show potential as anticancer drugs [1]. These heteroarotinoids control cell growth, differentiation, and apoptosis of the cancer cells. Heteroarotinoids were originally derived from an arotinoid class related to retinoids by strategically placing a heteroatom (O,N,S) in the molecular framework of a saturated six-membered ring [27]. This modification in the cyclohexyl ring reduced the toxicity of analogs of several the natural retinoids, including all-trans retinoic acid, by 1000-fold and thus showed promising activity against a variety of cancer cells [2-10].Based on structure-activity relationships (SAR), various Hets have been synthesized with several displaying significant anticancer activity [4-10].Further structural modifications led to a related class of compounds known as Flexible Heteroarotinoids (Flex-Hets) in which certain linking groups situated between a saturated heterocyclic ring and an aryl group were altered. It was discovered that by including more flexible urea and thiourea linkers the anticancer activity increased markedly.1 Consequently, the introduction of a thiourea linker not only provided flexibility between the ring systems, but also increased the scope of activity of the drug against a series of cancer cells lines including breast, head-neck, kidneys, lung and certain ovarian cancers [1,3-6,8,9].