Anticarcinogenic and antioxidant activity of diindolylmethane derivatives

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:suanqing
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AIM: To investigate the synthesis methods and the bioactivity of diindolylmethane (DIM) derivatives. METHODS:1) A 3D-Quantitative Structure-Active Relationships (QSAR) Comparative Molecular Field Analysis (CoMFA) studyof 14 DIM derivatives was investigated to predict their anticarcinogenic activity. 2) Based on CoMFA model, aseries of new derivatives of DIM were designed and synthesized. 3) Their free radical scavenging and antioxidantpotentials were tested using in-vitro DPPH radical scavenging and b-carotene antioxidant models. 4) Theanticarcinogenic activities of some compounds were tested by using microculture tetrazolium assay (MTT) andsulforhodamine B (SRB) proteochromosomic assays. RESULTS: 1) The CoMFA model derived from DIM ana-logues proved a good predictive ability with q2 value of 0.827. 2) New designed compounds 3c and 4c exhibited3-fold more potent radical scavenging activity than reference substance Vitamin E in DPPH model expressed by IC50values. 3) The primary antitumor screening essay showed that some DIM derivatives designed exhibited theinhibitory activities to some tumor cell growth at relatively high concentration, and DIM was the most effectiveamong them. CONCLUSION: DIMs 3D-QSAR model is reliable. According to it, eleven DIM derivatives weresynthesized, and two derivatives of them possess potent radical scavenging activities and some showed the inhibi-tory activities in primary anticancer assay in vitro. METHODS: 1) A 3D-Quantitative Structure-Active Relationships (QSAR) Comparative Molecular Field Analysis (CoMFA) study of 14 DIM derivatives was investigated to predict their anticarcinogenic activity 3) Their free radical scavenging and antioxidant potentials were tested using in-vitro DPPH radical scavenging and b-carotene antioxidant models. 4) Theanticarcinogenic activities of some compounds RESULTS: The CoMFA model derived from DIM ana-logues proved a good predictive ability with q2 value of 0.827. 2) New designed compounds 3c and 4c exhibited 3-fold more potent radical scavenging activity than reference substance Vitamin E in DPPH model expressed by IC50 values. 3) The primary a ntitumor screening essay showed that some DIM derivatives designed presenting thehibitory activities to some tumor cell growth at relatively high concentration, and DIM was the most effectiveamong them. CONCLUSION: DIMs 3D-QSAR model is reliable. According to it, eleven DIM derivatives weresynthesized, and two derivatives of them possess potent radical scavenging activities and some showed the inhibi-tory activities in primary anticancer assay in vitro.
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