Targeted Isolation of N-Acetylcysteine-Containing Angucycline Derivatives from Streptomyces sp. MC16 and Their Antiproliferative Effects

Jun Gu Kim; Byeongsan Lee; Jae Sang Han; Taehoon Oh; Beomcheol Park; Yong Beom Cho; Beom Kyun An; Jin Won Choi; Sung-Kyun Ko; Mi Kyeong Lee; Young-Soo Hong; Bang Yeon Hwang

doi:10.1021/acsomega.3c04647

Targeted Isolation of N-Acetylcysteine-Containing Angucycline Derivatives from Streptomyces sp. MC16 and Their Antiproliferative Effects

ACS Omega. 2023 Oct 6;8(41):38263-38271. doi: 10.1021/acsomega.3c04647. eCollection 2023 Oct 17.

Authors

Jun Gu Kim¹, Byeongsan Lee^{1

2}, Jae Sang Han¹, Taehoon Oh^{1

2}, Beomcheol Park^{1

2}, Yong Beom Cho¹, Beom Kyun An¹, Jin Won Choi³, Sung-Kyun Ko², Mi Kyeong Lee¹, Young-Soo Hong², Bang Yeon Hwang¹

Affiliations

¹ College of Pharmacy, Chungbuk National University, Cheongju 28160, South Korea.
² Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, South Korea.
³ Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.

Abstract

Liquid chromatography-mass spectrometry (LC-MS/MS)-based molecular networking analysis was applied to Streptomyces sp. MC16. The automatic classification of the MolNetEnhancer module revealed that its major constituent was an angucycline derivative. By targeted isolation of unique clusters in the molecular network, which showed different patterns from typical angucycline compounds, two new N-acetylcysteine-attached angucycline derivatives (1 and 2) were isolated. The structures were elucidated based on intensive NMR analysis and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). All isolated compounds (1-4) were tested for their inhibitory effects on the proliferation of A431, A549, and HeLa cell lines. Antibiotics 100-1 (3) and vineomycinone B₂ (4) showed moderate inhibitory effects on these three cell lines with IC₅₀ values ranging from 18.5 to 59.0 μM, while compounds 1 and 2 with an additional N-acetylcysteine residue showed weak inhibitory effects only on the HeLa cell line with IC₅₀ values of 54.7 and 65.2 μM, respectively.