Tiquizium Bromide

Arylmethylene derivatives, chromenes and aminothiophenes were synthesized from 2‐cyano‐N‐(4‐(3‐(thiophen‐2‐yl)acryloyl)phenyl)acetamide 2. The anticancer activity of most synthetic compounds was assessed in breast cancer (MCF‐7), hepatocellular carcinoma (HepG‐2) and cervical cancer (HeLa), with five of arylmethylene and chromene derivatives showing highest cytotoxic activity. Further, treatment of breast cancer (MCF‐7) cell lines with 4 d and 6 b, the most cytotoxic compounds; revealed down regulation for ERK‐2 protein with expression concentration; 527.7±6.61 and 427.7±8.39 pg/ml, respectively compared to staurosporine; 440.9±5.02 pg/ml. Moreover, cell death induction was assessed by Annexin V‐ FITC/PI assay and these compounds caused cell death by apoptosis, besides the DNA fragmentation was assessed by gel electrophoresis and ELISA and the data showed increase in the percentage of fragmentation in treated MCF‐7 of values; 30.49 % and 28.19 % in 4 d and 6 b, respectively confirming the same effect as staurosporine. The DNA‐flow cytometric cell cycle analysis showed that 4 d and 4 g arrested the cell cycle at S phase and 8 b arrested it at G1/S phase. Molecular docking was carried out together with physicochemical properties prediction using DruLiTo program.

Thiophene and its substituted derivatives are very important class of heterocyclic compounds which shows interesting applications in the field of medicinal chemistry. It has made an indispensable anchor for medicinal chemists to produce combinatorial library and carry out exhaustive efforts in the search of lead molecules. It has been reported to possess a wide range of therapeutic properties with diverse applications in medicinal chemistry and material science, attracting great interest in industry as well as academia. It has been proven to be effectual drugs in present respective disease scenario. They are remarkably effective compounds both with respect to their biological and physiological functions such as anti-inflammatory, anti-psychotic, anti-arrhythmic, anti-anxiety, anti-fungal, antioxidant, estrogen receptor modulating, anti-mitotic, anti-microbial, kinases inhibiting and anti-cancer. Thus the synthesis and characterization of novel thiophene moieties with wider therapeutic activity is a topic of interest for the medicinal chemist to synthesize and investigate new structural prototypes with more effective pharmacological activity. However, several commercially available drugs such as Tipepidine, Tiquizium Bromides, Timepidium Bromide, Dorzolamide, Tioconazole, Citizolam, Sertaconazole Nitrate and Benocyclidine also contain thiophene nucleus. Therefore, it seems to be a requirement to collect recent information in order to understand the current status of the thiophene nucleus in medicinal chemistry research.