stilbenes and benzothiophene

Selective estrogen receptor modulators (SERMs), known previously as "antiestrogens", are a new category of therapeutic agents used for the prevention and treatment of diseases such as osteoporosis and breast cancer. SERMs act as ER-agonist in some tissues while acting as ER-antagonist in others based on conformational change of the receptors, particularly at the helix 12. Currently, there are two classes of clinically approved SERMs; triphenylethylene derivatives (e.g., tamoxifen) and benzothiophene derivatives (e.g., raloxifene). Tamoxifen, raloxifene and toremifene are the most widely used SERMs. Tamoxifen, an antagonist of the breast tissue, is the first clinically identified compound with noticeable SERM activity. Although tamoxifen has been very successful in breast cancer treatment, its agonistic effect on the uterus is said to be associated with increase risk of developing endometrial cancer. Ideally, it is presumed that SERMs should selectively act as an agonist in the bone and brain while simultaneously acting as an antagonist in the breast and uterus. Therefore, the therapeutic goal of SERMs is the prevention of estrogen deficiency diseases without promoting estrogen-associated tumor growth. Therefore, the objective of this review is to summarize various effects that have been applied in improving the tissue-selectivity of SERMs, highlighting the emerging understanding of their mechanism of actions in selected target tissues and the development of the SERMs. The significance in recent discovery of selective estrogen receptor alpha modulators, SERAMs will also be reviewed.

Topics: Breast Neoplasms; Drug Design; Estrogen Receptor alpha; Female; Humans; Raloxifene Hydrochloride; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Stilbenes; Structure-Activity Relationship; Tamoxifen; Thiophenes; Toremifene

Herein, a light-activatable photosensitizer based on a diarylethene derivative, DAE-TPE, was developed for photodynamic therapy. Upon UV exposure, the "opened" form (OF) of DAE-TPE NPs was converted to the "closed" form (CF), and photosensitization was activated. The CF of DAE-TPE NPs exhibited sufficient photodynamic therapy effects upon HeLa cells.

Topics: Antineoplastic Agents; Ethylenes; Fluorescence Resonance Energy Transfer; HeLa Cells; Humans; Light; Molecular Conformation; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Stilbenes; Thiophenes

Heteroaromatic analogs of DMU-212 (8-15) have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. These novel analogs contain a trans-3,4,5-trimethoxystyryl moiety attached to the C2 position of indole, benzofuran, benzothiazole or benzothiophene ring (8, 11, 13 and 14, respectively) and showed potent growth inhibition in 85% of the cancer cell lines examined, with GI50 values <1 μM. Interestingly, trans-3,4- and trans-3,5-dimethoxystyryl DMU-212 analogs 9, 10, 12 and 15 exhibited significantly less growth inhibition than their 3,4,5-trimethoxystyryl counterparts, suggesting that the trans-3,4,5-trimethoxystyryl moiety is an essential structural element for the potent anti-cancer activity of these heterocyclic DMU-212 analogs. Molecular modeling studies showed that the four most active compounds (8, 11, 13 and 14) all bind to the colchicine binding site on tubulin, and that their binding modes are similar to that of DMU-212.

Topics: Antineoplastic Agents; Benzofurans; Benzothiazoles; Binding Sites; Cell Line, Tumor; Cell Survival; Colchicine; Drug Screening Assays, Antitumor; Humans; Molecular Docking Simulation; Protein Structure, Tertiary; Resveratrol; Stilbenes; Thiophenes; Tubulin

A novel series of combretastatin A-4 heterocyclic analogues was prepared by replacement of the B ring with indole, benzofurane or benzothiophene, attached at the C2 position. These compounds were evaluated for their abilities to inhibit tubulin assembly: derivative cis3b, having a benzothiophene, showed an activity similar to those of colchicine or deoxypodophyllotoxine. The antiproliferative and antimitotic properties of cis3b against keratinocyte cancer cell lines were also evaluated and the intracellular organization of microtubules in the cells after treatment with both stereoisomers of 3b was also determined, using confocal microscopy.

Topics: Antimitotic Agents; Benzofurans; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Colchicine; Heterocyclic Compounds; Humans; Indoles; Microscopy, Confocal; Microtubules; Stereoisomerism; Stilbenes; Thiophenes