Cytotoxic and Optically Active Pyrisulfoxins From the Endophytic Streptomyces albolongus EA12432

Abstract

R-Pyrisulfoxin C (1), S-pyrisulfoxin D [(+)-2], R-pyrisulfoxin D [(–)-2], pyrisulfoxin E (13), S-pyrisulfoxin F [(+)-14], and R-pyrisulfoxin F [(–)-14], six new caerulomycin derivatives with a 2,2′-bipyridine skeleton, were obtained from the cultures of the endophytic Streptomyces albolongus EA12432 with Aconitum carmichaeli (Ranunculaceae). Additionally, the racemic pyrisulfoxins A [(±)-3] and B [(±)-4] were further purified as optically pure compounds and identified the configurations for the first time. The racemic pyrisulfoxin D [(±)-2] displayed significant cytotoxicity against a series of cancer cell lines with IC50 values ranging from 0.92 to 9.71 μM. Compounds 7, 8, and (±)-3 showed cytotoxicity against the HCT-116, HT-29, BXPC-3, P6C, and MCF-7 cell lines. Notably, compounds 7 and 8 have a strong inhibition both on the proliferation of human colon cancer cells HCT-116 and HT-29 with IC50 values ranging from 0.048 to 0.2 μM (doxorubicin, 0.21 and 0.16 μM), and compound 1 showed a selective inhibition on the proliferation of the gastric carcinoma cell lines, N87, with an IC50 value of 8.09 μM. Optically pure compounds R(–)-14 and S(+)-14 showed weak cytotoxicity against HCT-116 and MCF-7 cell lines with the IC50 values of 14.7 μM and 10.4 μM, respectively. Interestingly, compounds 1 and (±)-2 didn't show cytotoxic activity against two human normal cell lines, HEK-293F and L02, with IC50 values >100 μM.