Synthesis of novel artesunate-benzothiophene and artemisinin-benzothiophene derivatives.

Natural products are used for the treatment of a variety of diseases for many years. Last decades, design and synthesis of novel biologically active hybrid molecules including natural product is gained big importance due to their unique and new biological properties. In the present study, novel artemisinin-benzothiophene derivatives (12 A-F) are synthesised. Initially, benzothiophene derivatives (4 A-4F) are prepared via the Pd-catalyzed coupling reactions and iodocyclisation reactions. Then, Suzuki-Miyaura coupling reactions were used for the formation of intermediates 6 A-6F (between 64% and 91% yields). Finally, the Steglich esterification reaction between intermediate 6 and artesunate formed the artemisinin-benzothiophene hybrids (9 A-9F) in moderate to excellent yields under very mild reaction conditions. When intermediate 6 was reacted with dihydroartemisinin, product 12 A-12F was also obtained with high yields.[Formula: see text].

Design, synthesis and pharmacological evaluation of novel Artemisinin-Thymol.

A molecular hybridization of natural products is a new concept in drug discovery and having critical roles to design new molecules with improved biological properties. Hybrid molecules display higher biological activities when compared to the parent drugs. In the present study, two natural products (thymol and artemisinin (ART)) are used for the synthesis of new hybrid thymol-artemisinin. After characterization, the cytotoxic activity of ART-thymol was tested against different cancer cell lines and non-cancerous human cell line. ART-Thymol show the cytotoxic effect with EC50 values 70,96µM for HepG2, 97,31µM for LnCap, 6,03µM for Caco-2, 77,98µM for HeLa and 62,28µM for HEK293 cells, respectively. Moreover, ART-Thymol was checked for drug-likeness, and the kinase inhibitory activity. ART-Thymol is investigated by using molecular docking. The results of qPCR was indicated CDK2 and P38 were inhibited by ART-Thymol. These results improved that thymol-artemisinin may be new candidates as an anticancer agents.

Identification of 3-Bromo-1-Ethyl-1H-Indole as a Potent Anticancer Agent with Promising Inhibitory Effects on GST Isozymes.

BACKGROUND: Indole-based heterocyclic compounds play important roles in pharmaceutical chemistry due to their unexpected biological and pharmacological properties. OBJECTIVE: Herein, we describe novel biological properties (antioxidant, antimicrobial and anti-cancer) of 3- bromo-1-ethyl-1H-indole (BEI) structure. METHODS: BEI was synthesized from 1-Methyl-2-phenylindole and N-bromosuccinimide and was characterized by using 1H and 13C NMR. Cytotoxicity was determined by MTT assay. Apoptosis analysis of BEI was determined by Arthur™ image-based Cytometer. Different methods were applied to assess the antioxidant activity of BEI. Molecular docking studies were conducted to determine the interactions of bonding between GST isozymes and BEI. RESULTS: According to the antioxidant and antimicrobial activity assays, BEI compound showed reduced total antioxidant activity compared to the Trolox standard, whereas it showed moderate antimicrobial activity against Aspergillus niger and Phytophora eryhtrospora. Notably, the BEI compound demonstrated substantial selective cytotoxicity for the first time towards cancer cell lines, and there existed a significant decrease in the percentage of live cells treated with BEI, in comparison to the control ones. Interestingly, BEI exhibited a promising glutathione S-transferase isozymes inhibition. CONCLUSION: The results of this study suggest that BEI seems to be a promising molecule to be used in the design of new anti-cancer agents that provide superiority to present commercial anti-cancer drugs.