Synthesis and cytotoxic activity of MOM-ether analogs of isosteviol.
Lung cancer is one of the most common malignancies worldwide. In this Letter, novel MOM-ether analogs of isosteviol were designed and synthesized to be tested for anticancer activities against H1299 lung cancer cell lines. The effects of these derivatives were studied in H1299 human large cell lung carcinoma cells that are null for p53 and compared to normal counterparts NL-20 normal lung epithelial cells. The initial screening of twelve MOM-ether analogs of isosteviol derivatives on H1299 lung cancer cells by MTT assay revealed that two derivatives (an ester and a carbamate) were the most potent in reducing cell viability. The IC50 values for these derivatives were determined to be 14 and 21 μM respectively. We compared the cytotoxicity of the best derivatives in H1299 lung cancer cells and NL-20 normal lung epithelial cells. Both derivatives showed lower cytotoxic effects on NL-20 normal lung epithelial cells. Moreover, both derivatives induced apoptosis in H1299 lung cancer cells more than NL-20 normal lung epithelial cells.
Department of Health Sciences, Biomedical Program College of Arts and Sciences, Qatar University, Doha, Qatar; Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Ahmed
A
Malki
Department of Chemistry & Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Rumita
R
Laha
Department of Chemistry & Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA. Electronic address: bergmeis@ohio.edu.
Stephen C
SC
Bergmeier
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004987:Ethers / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D004987:Ethers; C515747:isosteviol
Anticancer; Diterpene; Isosteviol; Lung cancer; p53