Xuetonglactones A-F: Highly Oxidized Lanostane and Cycloartane Triterpenoids From Kadsura heteroclita Roxb. Craib

Nuzhat Shehla; Bin Li; Liang Cao; Jianping Zhao; Yuqing Jian; Muhammad Daniyal; Atia-Tul Wahab; Ikhlas A Khan; Duan-Fang Liao; Atta-Ur Rahman; M Iqbal Choudhary; Wei Wang

doi:10.3389/fchem.2019.00935

Xuetonglactones A-F: Highly Oxidized Lanostane and Cycloartane Triterpenoids From Kadsura heteroclita Roxb. Craib

Front Chem. 2020 Jan 21:7:935. doi: 10.3389/fchem.2019.00935. eCollection 2019.

Authors

Nuzhat Shehla^{1

2}, Bin Li^{1

2}, Liang Cao¹, Jianping Zhao³, Yuqing Jian¹, Muhammad Daniyal¹, Atia-Tul Wahab⁴, Ikhlas A Khan³, Duan-Fang Liao¹, Atta-Ur Rahman², M Iqbal Choudhary^{1

2

4}, Wei Wang^{1

2}

Affiliations

¹ TCM and Ethnomedicine Innovation and Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.
² International Center for Chemical and Biological Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi, Pakistan.
³ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS, United States.
⁴ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

Abstract

Xuetonglactones A-F (1-6), six unreported highly oxidized lanostane- and cycloartane-type triterpenoids along with 22 known scaffolds (7-28) were isolated from the stems of Kadsura heteroclita (Roxb.) Craib. Compared with previous congeners, xuetonglactone A (1), possesses an unprecedented 20,21-α-epoxide, and xuetonglactone D (4) features an unusual 19-α-hydroperoxyl moiety. The structures and the absolute configurations of the compounds were established by extensive one- and two-dimensional NMR, and electronic circular dichroism (ECD) spectroscopic analysis, with those of 1 and 5 confirmed by single-crystal X-ray diffraction technique. Compounds 1 and 2 exhibited inhibition of iNOS activity in LPS-induced macrophages with IC₅₀ values of 22.0, and 17.0 μg/mL, respectively. While compounds 6, 7, 8, and 24 showed potent cytotoxic activities against human cervical cancer cell lines (HeLa) with the IC₅₀ values of 4.0, 5.8, 5.0, and 6.4 μM, and against human gastric cancer cells (BGC 823) with the IC₅₀ values of 2.0, 5.0, 2.5, and 2.0 μM, respectively. Moreover, plausible biogenetic pathways of (1-6) were also proposed.

Keywords: Kadsura heteroclita; cytotoxicity; highly oxidized; lanostane triterpenoids; xuetonglactones.