trichodermamide-b and Colorectal-Neoplasms

The trichodermamides are modified dipeptides isolated from a wide variety of fungi, including Trichoderma virens. Previous studies reported that trichodermamide B (2) initiated cytotoxicity in HCT-116 colorectal cancer cells, while trichodermamide A (1) was devoid of activity. We recently developed an efficient total synthesis for the trichodermamides A-C (1-3). Multiple intermediates and analogues were produced, and they were evaluated for biological effects to identify additional structure-activity relationships and the possibility that a simplified analogue would retain the biological effects of 2. The antiproliferative effects of 18 compounds were evaluated, and the results show that 2 and four other compounds are active in HeLa cells, with IC

Topics: Antineoplastic Agents; Cell Cycle; Colorectal Neoplasms; Dipeptides; Diterpenes; DNA; Fungi; HeLa Cells; Humans; Marine Biology; Molecular Structure; S Phase; Structure-Activity Relationship

Chemical investigations of a culture broth from the endophytic fungus Eupenicillium sp. afforded the new modified dipeptide trichodermamide C 1. The structure of 1 was established following the analysis of NMR, UV, IR, MS and X-ray diffraction data. Trichodermamide C was shown by high content screening to display cytotoxicity towards the human colorectal carcinoma HCT116 and human lung carcinoma A549 with IC(50) values of 0.68 and 4.28microg/ml, respectively.

Topics: Antineoplastic Agents; Colorectal Neoplasms; Dipeptides; Diterpenes; Eurotiales; Humans; Inhibitory Concentration 50; Lung Neoplasms; Penicillium; Spectrum Analysis; X-Ray Diffraction