Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl Benzimidazole and Benzothiazole derivatives.
Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β'-Acetoxy-5β'-hydroxy-6'-B-norcholesteryl)benzimidazole (9b) with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. cuijg1954@126.com.|Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Qizhou University, Qizhou 535099, China. cuijg1954@126.com.
Jianguo
J
Cui
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. 554377663@qq.com.
Binbin
B
Qi
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. ganchunfang2008@126.com.
Chunfang
C
Gan
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. 573052962@qq.com.
Zhipin
Z
Liu
Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Qizhou University, Qizhou 535099, China. mrhuanghu@126.com.
Hu
H
Huang
Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Qizhou University, Qizhou 535099, China. linqifu335@163.com.
Qifu
Q
Lin
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. 404045774@qq.com.
Dandan
D
Zhao
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China. huangyanmin828@163.com.
Yanmin
Y
Huang
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002788:Cholesterol Esters / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007564:Japan; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011161:Porifera / Q000737:chemistry / Q000254:growth & development; D013237:Stereoisomerism; D013261:Sterols / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C000603852:2-(3'-acetoxy-5'-hydroxy-6'-B-norcholesteryl)benzimidazole; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D052160:Benzothiazoles; D002788:Cholesterol Esters; D013261:Sterols; D002784:Cholesterol