Cytotoxic Indolocarbazoles From a Marine-Derived Streptomyces Sp. OUCMDZ-5380

Tongxu Cui; Simin Lin; Zizhen Wang; Peng Fu; Cong Wang; Weiming Zhu

doi:10.3389/fmicb.2022.957473

Cytotoxic Indolocarbazoles From a Marine-Derived Streptomyces Sp. OUCMDZ-5380

Front Microbiol. 2022 Jul 12:13:957473. doi: 10.3389/fmicb.2022.957473. eCollection 2022.

Authors

Tongxu Cui¹, Simin Lin¹, Zizhen Wang¹, Peng Fu^{1

2}, Cong Wang³, Weiming Zhu^{1

2}

Affiliations

¹ Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
² Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China.
³ Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning, China.

Abstract

Under the guidance of global natural product social molecular networking, three new indolocarbazoles named streptocarbazoles F-H (1-3), along with staurosporine (4) were isolated from the marine-derived Streptomyces sp. OUCMDZ-5380. Structures of streptocarbazoles F-H were, respectively, determined as N-demethyl-N-hexanoylstaurosporine (1), N-demethyl-N-(2-methyl-3-methoxypyridin-4-yl) staurosporine staurosporine (2), and 4-(N-demethylstaurosporine-N-yl)-1,2-dimethyl-3-methoxypyridinium (3) by spectroscopic analysis and electronic circular dichroism comparison with staurosporine. Compared with staurosporine (4), streptocarbazoles F-H (1-3) showed a selective antiproliferation of the acute myeloid leukemia cell line MV4-11 with the IC₅₀ values of 0.81, 0.55, and 1.88 μM, respectively.

Keywords: Streptomyces sp.; antiproliferatory activity; indolocarbazoles; marine microorganism; streptocarbazoles F–H.