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 IC 50 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 IC 50 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 IC 50 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 IC 50 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 IC 50 values >100 µM.

Source, Synthesis, and Biological Evaluation of Natural Occurring 2,2′‐Bipyridines

“…Caerulomycins (CAEs), collismycins (COLs), and related derivatives are widely explored for various biological activities. CAEs have been shown to have antibacterial, antitumor, and notable immunosuppressive activities, while COLs have been shown to have anti‐cancer, anti‐inflammatory, and neuroprotective properties [8] . In this review, an effort has been made to demonstrate the isolation, synthesis, and biological properties of naturally occurring 2,2′‐bipyridine reported in the literature.…”