Cytotoxic and Optically Active Pyrisulfoxins From the Endophytic Streptomyces albolongus EA12432

Yuqi Du; Chen Wang; Guodong Cui; Yiwen Chu; Qian Jia; Yi Wang; Weiming Zhu

doi:10.3389/fchem.2020.00248

Cytotoxic and Optically Active Pyrisulfoxins From the Endophytic Streptomyces albolongus EA12432

Front Chem. 2020 May 6:8:248. doi: 10.3389/fchem.2020.00248. eCollection 2020.

Authors

Yuqi Du¹, Chen Wang¹, Guodong Cui¹, Yiwen Chu², Qian Jia¹, Yi Wang¹, Weiming Zhu^{1

3}

Affiliations

¹ Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
² Sichuan Industrial Institute of Antibiotics, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, China.
³ Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology, Qingdao, China.

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.

Keywords: 2; 2′-bipyridine; Aconitum carmichaeli; Streptomyces albolongus; cytotoxicity; endophyte.