Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structure Elucidation
2.2. Cytotoxicity Evaluation
2.3. Discussion
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Chemicals and Ingredients
3.3. Fungal Strains and Culture Media
3.4. Microbial Screening Procedure
3.5. Microbial Transformation of Yakuchinone A
3.6. Preparation of Mosher’s Esters
3.7. Hydrolysis of Compounds 4, 8, and 9
3.8. Cytotoxicity Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Li, Y.; Tan, Y.; Cai, H.; Zhang, J. Metabonomic study of the fruits of Alpinia oxyphylla as an effective treatment for chronic renal injury in rats. J. Pharm. Biomed. 2016, 124, 236–245. [Google Scholar] [CrossRef] [PubMed]
- Yuan, Y.; Tan, Y.; Xu, P.; Li, H.; Li, Y.; Chen, W.; Zhang, J.; Chen, F.; Huang, G. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility. Afr. J. Tradit. Complement. Altern. Med. 2014, 11, 120–125. [Google Scholar] [CrossRef] [Green Version]
- Chen, P.; Wang, P.; Jiao, Z.; Xiang, L. Sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-acetylcholinesterase activity. Helv. Chim. Acta 2014, 97, 388–397. [Google Scholar] [CrossRef]
- Hikino, H.; Kiso, Y.; Kato, N.; Hamada, Y.; Shioiri, T.; Aiyama, R.; Itokawa, H.; Kiuchi, F.; Sankawa, U. Antihepatotoxic actions of gingerol and diarylheptanoids. J. Ethnopharmacol. 1985, 14, 31–39. [Google Scholar]
- Yu, S.H.; Kim, H.J.; Jeon, S.Y.; Kim, M.R.; Lee, B.S.; Lee, J.J.; Kim, D.; Lee, Y.C. Anti-inflammatory and anti-nociceptive activities of Alpinia oxyphylla Miquel extracts in animal models. J. Ethnopharmacol. 2020, 260, 112985. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.J.; Kim, J.S.; Yoon, J.W.; Kim, H.; Ryu, J. Suppression of inducible nitric oxide synthase expression by yakuchinones and their analogues. Chem. Pharm. Bull. 2006, 54, 377–379. [Google Scholar] [CrossRef] [Green Version]
- Lin, R.; Yen, C.; Chou, T.; Chiang, F.; Wang, G.; Tseng, Y.; Wang, L.; Huang, T.; Wang, H.; Chan, L. Antioxidant, anti-adipocyte differentiation, antitumor activity and anthelmintic activities against Anisakis simplex and Hymenolepis nana of yakuchinone A from Alpinia oxyphylla. BMC Complement. Altern. Med. 2013, 13, 237. [Google Scholar] [CrossRef] [Green Version]
- Miyazawa, M.; Nakamura, Y.; Sakano, K.; Nakamura, S.I.; Kosaka, H. Suppression of SOS-inducing activity of chemical mutagens by yakuchinone A from Alpinia oxyphylla in the Salmonella typhimurium TA1535/pSK1002 umu test. J. Oleo Sci. 2001, 50, 485–489. [Google Scholar] [CrossRef] [Green Version]
- Kiuchi, F.; Iwakami, S.; Shibuya, M.; Hanaoka, F.; Sankawa, U. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. Chem. Pharm. Bull. 1992, 40, 387–391. [Google Scholar] [CrossRef] [Green Version]
- Chun, K.S.; Park, K.K.; Lee, J.; Kang, M.; Surh, Y.J. Inhibition of mouse skin tumor promotion by anti-inflammatory diarylheptanoids derived from Alpinia oxyphylla Miquel (Zingiberaceae). Oncol. Res. 2002, 13, 37–45. [Google Scholar] [CrossRef] [PubMed]
- Chun, K.S.; Sohn, Y.; Kim, H.S.; Kim, O.H.; Park, K.K.; Lee, J.M.; Lee, J.; Lee, J.Y.; Moon, A.; Lee, S.S.; et al. Anti-tumor promoting potential of naturally occurring diarylheptanoids structurally related to curcumin. Mutat. Res. 1999, 428, 49–57. [Google Scholar] [CrossRef]
- Hegazy, M.E.F.; Mohamed, T.A.; ElShamy, A.I.; Abou-El-Hamd, H.M.; Mahalel, U.A.; Reda, E.H.; Shaheen, A.M.; Tawfik, W.A.; Shahat, A.A.; Shams, K.A. Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review. J. Adv. Res. 2015, 6, 17–33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ponnusamy, S.; Zinjarde, S.; RaviKumar, A. Curcuminoid analogs via microbial biotransformation with improved therapeutic properties. In Food Biosynthesis; Grumezescu, A.M., Holban, A.M., Eds.; Elsevier: Amsterdam, The Netherlands, 2017; Volume 1, pp. 251–275. [Google Scholar]
- Venisetty, R.K.; Ciddi, V. Application of microbial biotransformation for the new drug discovery using natural drugs as substrates. Curr. Pharm. Biotechnol. 2003, 4, 153–167. [Google Scholar] [CrossRef] [PubMed]
- Bianchini, L.F.; Arruda, M.F.C.; Vieira, S.R.; Campelo, P.M.S.; Grégio, A.M.; Rosa, E.A.R. Microbial biotransformation to obtain new antifugals. Front. Microbiol. 2015, 6, 1433. [Google Scholar] [CrossRef] [Green Version]
- Perkins, C.; Siddique, S.; Puri, M.; Demain, A.L. Biotechnological applications of microbial bioconversions. Crit. Rev. Biotechnol. 2016, 36, 1050–1065. [Google Scholar] [CrossRef]
- Han, J.T.; Lee, S.Y.; Lee, Y.H.; Baek, N.I. Antioxidative diarylheptanoids from the fruits of Alpinia oxyphylla. Food Sci. Biotechnol. 2007, 16, 1060–1063. [Google Scholar]
- Su, B.; Park, E.J.; Mbwambo, Z.H.; Santarsiero, B.D.; Mesecar, A.D.; Fong, H.H.S.; Pezzuto, J.M.; Kinghorn, A.D. New chemical constituents of Euphorbia quinquecostata and absolute configuration assignment by a convenient mosher ester procedure carried out in NMR tubes. J. Nat. Prod. 2002, 65, 1278–1282. [Google Scholar] [CrossRef]
- Nam, J.W.; Kang, G.Y.; Han, A.R.; Lee, D.; Lee, Y.S.; Seo, E.K. Diarylheptanoids from the seeds of Alpinia katsumadai as heat shock factor 1 inducers. J. Nat. Prod. 2011, 74, 2109–2115. [Google Scholar] [CrossRef]
- Li, J.; Zhao, F.; Li, M.Z.; Chen, L.X.; Qiu, F. Diarylheptanoids from the rhizomes of Curcuma kwangsiensis. J. Nat. Prod. 2010, 73, 1667–1671. [Google Scholar] [CrossRef]
- Seco, J.; Quiñoá, E.; Riguera, R. Assignment of the absolute configuration of polyfunctional compounds by NMR using chiral derivatizing agents. Chem. Rev. 2012, 112, 4603–4641. [Google Scholar] [CrossRef]
- Freire, F.; Seco, J.M.; Quinoá, E.; Riguera, R. Determining the absolute stereochemistry of secondary/secondary diols by 1H NMR: Basis and applications. J. Org. Chem. 2005, 70, 3778–3790. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Z.; Sun, S.; Yu, Y.; Mándi, A.; Luo, J.; Yang, M.; Kurtán, T.; Chen, W.; Shen, L.; Wu, J. Discovery of benthol A and its challenging stereochemical assignment: Opening up a new window for skeletal diversity of super-carbon-chain compounds. Chem. Sci. 2021, 12, 10197–10206. [Google Scholar] [CrossRef] [PubMed]
- Han, C.; Yamano, Y.; Kita, M.; Takamura, H.; Uemura, D. Determination of absolute configuration of C14–C23 fragment in symbiodinolide. Tetrahedron Lett. 2009, 50, 5280–5282. [Google Scholar] [CrossRef]
- Yang, Y.; Zhang, J.; Liu, Y.; Tang, Q.; Zhao, Z.; Xia, W. Structural elucidation of a 3-O-methyl-D-galactose-containing neutral polysaccharide from the fruiting bodies of Phellinus igniarius. Carbohydr. Res. 2007, 342, 1063–1070. [Google Scholar] [CrossRef]
- Köllmann, C.; Jones, P.G.; Werz, D.B. Synthesis of 5-C-methylated D-mannose, D-galactose, L-gulose, and L-altrose and their structural elucidation by NMR spectroscopy. Org. Lett. 2018, 20, 1220–1223. [Google Scholar] [CrossRef]
- Gubica, T.; Temeriusz, A.; Paradowska, K.; Ostrowski, A.; Klimentowska, P.; Cyrański, M.K. Single-crystal and powder X-ray diffraction and solid-state 13C NMR of p-nitrophenyl glycopyranosides, the derivatives of D-galactose, D-glucose, and D-mannose. Carbohydr. Res. 2009, 344, 1734–1744. [Google Scholar] [CrossRef]
- de María, P.D.; de Gonzalo, G.; Alcántara, A.R. Biocatalysis as useful tool in asymmetric synthesis: An assessment of recently granted patents (2014–2019). Catalysts 2019, 9, 802. [Google Scholar] [CrossRef] [Green Version]
- Albarrán-Velo, J.; González-Martínez, D.; Gotor-Fernández, V. Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks. Biocatal. Biotransform. 2018, 36, 102–130. [Google Scholar] [CrossRef] [Green Version]
- Borges, K.B.; de Souza Borges, W.; Durán-Patrón, R.; Pupo, M.T.; Bonato, P.S.; Collado, I.G. Stereoselective biotransformations using fungi as biocatalysts. Tetrahedron Asymmetry 2009, 20, 385–397. [Google Scholar] [CrossRef]
- Kozłowska, E.; Urbaniak, M.; Kancelista, A.; Dymarska, M.; Kostrzewa-Susłow, E.; Stępień, Ł.; Janeczko, T. Biotransformation of dehydroepiandrosterone (DHEA) by environmental strains of filamentous fungi. RSC Adv. 2017, 7, 31493–31501. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Z.X.; Li, Z.H.; Yin, W.B.; Li, S.M. Biosynthesis of viridicatol in Penicillium palitans implies a cytochrome P450-mediated meta hydroxylation at a monoalkylated benzene ring. Org. Lett. 2022, 24, 262–267. [Google Scholar] [CrossRef] [PubMed]
- Rocha, B.A.; Pupo, M.T.; Antonucci, G.A.; Sampaio, S.V.; Paiva, R.M.A.; Said, S.; Gobbo-Neto, L.; Costa, F.B.D. Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus. J. Ind. Microbiol. Biotechnol. 2012, 39, 1719–1724. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Du, Z.; Wang, W.; Song, M.; Sanidad, K.; Sukamtoh, E.; Zheng, J.; Tian, L.; Xiao, H.; Liu, Z. Structure–activity relationship of curcumin: Role of the methoxy group in anti-inflammatory and anticolitis effects of curcumin. J. Agric. Food Chem. 2017, 65, 4509–4515. [Google Scholar] [CrossRef] [PubMed]
- Ali, M.S.; Banskota, A.H.B.; Tezuka, Y.; Saiki, I.; Kadota, A. Antiproliferative activity of diarylheptanoids from the seeds of Alpinia blepharocalyx. Chem. Pharm. Bull. 2001, 24, 525–528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, X.; Deng, Y.; Kurtz, N.C.; Sun, Y.; Xue, M.; Wu, X. Concise and efficient total synthesis of oxyphyllacinol, yakuchione-A and yakuchione-B. Synth. Commun. 2022. [Google Scholar] [CrossRef]
- Xiao, Y.; Han, F.; Lee, I.-S. Biotransformation of the phenolic constituents from licorice and cytotoxicity evaluation of their metabolites. Int. J. Mol. Sci. 2021, 22, 10109. [Google Scholar] [CrossRef] [PubMed]
- Han, F.; Xiao, Y.; Lee, I.-S. Microbial conjugation studies of licochalcones and xanthohumol. Int. J. Mol. Sci. 2021, 22, 6893. [Google Scholar] [CrossRef] [PubMed]
C No. | 2 | 3a | 3b | 4 | ||||
---|---|---|---|---|---|---|---|---|
δH a (J/Hz) | δC a | δH b (J/Hz) | δC b | δH b (J/Hz) | δC b | δH a (J/Hz) | δC a | |
1 | 2.55 m | 32.8 | 2.43 m | 31.1 | 2.43 m | 31.1 | 2.56 m | 31.2 |
2.67 m | 2.56 m | 2.56 m | 2.70 m | |||||
2 | 1.66 m | 40.7 | 1.54 m | 39.4 | 1.54 m | 39.4 | 1.69 m | 39.0 |
3 | 3.51 m | 71.8 | 3.34 | 69.0 | 3.34 | 69.1 | 3.51 m | 70.2 |
4 | 1.47 m | 38.4 | 1.32 m | 37.1 | 1.32 m | 37.1 | 1.47 m | 36.8 |
5 | 1.41 m | 26.5 | 1.33 m | 21.7 | 1.33 m | 21.7 | 1.37 m | 25.0 |
6 | 1.61 m | 32.9 | 1.57 m | 39.7 | 1.57 m | 39.7 | 1.61 m | 31.4 |
7 | 2.60 t (7.6) | 37.0 | 4.48 m | 72.4 | 4.48 m | 72.3 | 2.60 m | 35.5 |
1′ | - | 135.5 | - | 133.3 | - | 133.3 | - | 137.5 |
2′ | 6.75 d (1.8) | 113.3 | 6.70 d (1.8) | 112.4 | 6.70 d (1.8) | 112.4 | 6.84 d (1.8) | 112.6 |
3′ | - | 148.9 | - | 147.3 | - | 147.3 | - | 149.3 |
4′ | - | 144.0 | - | 144.3 | - | 144.3 | - | 144.6 |
5′ | 6.69 d (8.0) | 116.2 | 6.65 d (8.1) | 115.2 | 6.64 d (8.1) | 115.2 | 7.08 d (8.3) | 116.9 |
6′ | 6.61 dd | 121.9 | 6.54 dd | 120.2 | 6.54 dd | 120.2 | 6.74 dd | 120.5 |
(8.0, 1.8) | (8.1, 1.8) | (8.1, 1.8) | (8.3, 1.8) | |||||
1″ | - | 145.6 | - | 146.5 | - | 146.5 | - | 142.4 |
2″ | 7.14 | 129.5 | 7.30 d (4.4) | 125.8 | 7.29 d (4.6) | 125.8 | 7.15 | 128.0 |
3″ | 7.23 | 129.4 | 7.30 d (4.4) | 127.9 | 7.29 d (4.6) | 127.9 | 7.23 | 127.8 |
4″ | 7.12 | 126.8 | 7.20 m | 126.5 | 7.20 m | 126.5 | 7.13 | 125.3 |
5″ | 7.23 | 129.4 | 7.30 d (4.4) | 127.9 | 7.29 d (4.6) | 127.9 | 7.23 | 127.8 |
6″ | 7.14 | 129.5 | 7.30 d (4.4) | 125.8 | 7.29 d (4.6) | 125.8 | 7.15 | 128.0 |
1‴ | - | - | - | - | - | - | 4.83 d (7.7) | 101.7 |
2‴ | - | - | - | - | - | - | 3.48 m | 73.5 |
3‴ | - | - | - | - | - | - | 3.46 m | 76.4 |
4‴ | - | - | - | - | - | - | 3.39 m | 69.9 |
5‴ | - | - | - | - | - | - | 3.38 m | 76.7 |
6‴ | - | - | - | - | - | - | 3.69 m | 61.1 |
3.87 m | ||||||||
3-OH | - | - | 4.32 d (4.4) | - | 4.32 d (4.4) | - | - | - |
7-OH | - | - | 5.07 d (4.4) | - | 5.07 d (4.4) | - | - | - |
4′-OH | - | - | 8.60 s | - | 8.60 s | - | - | - |
3′-OCH3 | 3.81 s | 56.5 | 3.73 s | 55.5 | 3.72 s | 55.5 | 3.82 s | 55.3 |
C No. | 5 | 6 | 7 | 8 | 9 | |||||
---|---|---|---|---|---|---|---|---|---|---|
δH (J/Hz) | δC | δH (J/Hz) | δC | δH (J/Hz) | δC | δH (J/Hz) | δC | δH (J/Hz) | δC | |
1 | 2.52 m | 32.7 | 2.55 m | 32.8 | 2.53 m | 32.8 | 2.54 m | 32.9 | 2.62 m | 31.9 |
2.65 m | 2.66 m | 2.67 m | 2.68 m | |||||||
2 | 1.66 m | 40.7 | 1.63 m | 40.8 | 1.64 m | 40.8 | 1.69 m | 40.8 | 1.79 m | 37.5 |
3 | 3.51 m | 71.8 | 3.52 m | 71.8 | 3.58, m | 71.9 | 3.51 m | 71.9 | 3.69 m | 80.3 |
4 | 1.46 m | 38.4 | 1.48 m | 38.4 | 1.46 m | 38.6 | 1.47 m | 38.4 | 1.59 m | 37.0 |
5 | 1.44 m | 26.4 | 1.35m | 26.5 | 1.37 m | 26.8 | 1.37 m | 26.7 | 1.42 m | 26.0 |
6 | 1.56 m | 33.2 | 1.59 m | 32.8 | 1.58 m | 31.3 | 1.61 m | 31.5 | 1.63 m | 32.9 |
7 | 2.50 t | 36.1 | 2.53 t | 37.0 | 2.58 t | 31.3 | 2.64 m | 31.2 | 2.62 m | 36.0 |
(7.4) | (7.3) | (7.7) | 2.74 m | |||||||
1′ | - | 135.5 | - | 135.5 | - | 135.5 | - | 135.5 | - | 135.6 |
2′ | 6.75 d | 113.3 | 6.75 d | 113.3 | 6.75 d | 113.3 | 6.76 d | 113.3 | 6.79 d | 113.4 |
(1.4) | (1.6) | (1.7) | (1.8) | (1.8) | ||||||
3′ | - | 148.9 | - | 148.9 | - | 148.9 | - | 148.9 | - | 148.9 |
4′ | - | 145.5 | - | 145.6 | - | 145.5 | - | 145.5 | - | 145.5 |
5′ | 6.68 d | 116.2 | 6.69 d | 116.2 | 6.68 d | 116.2 | 6.69 d | 116.2 | 6.69 d | 116.2 |
(7.8) | (8.0) | (8.0) | (8.1) | (7.9) | ||||||
6′ | 6.62 dd | 121.9 | 6.60 | 121.9 | 6.62 dd | 121.9 | 6.62 dd | 121.9 | 6.62 dd | 121.9 |
(7.8, 1.4) | (8.0, 1.7) | (8.1, 1.8) | (7.9, 1.8) | |||||||
1″ | - | 134.9 | - | 145.6 | - | 130.3 | - | 133.6 | - | 144.2 |
2″ | 6.97 d (8.1) | 130.4 | 6.60 | 116.4 | - | 156.4 | - | 157.1 | 7.15 | 129.4 |
3″ | 6.67 d (8.1) | 116.2 | - | 158.4 | 6.71 | 116.0 | 7.11 | 116.4 | 7.23 | 129.6 |
4″ | - | 156.4 | 6.57 dd | 113.7 | 6.96 td | 120.6 | 6.91 m | 123.3 | 7.11 | 126.7 |
(7.9, 2.1) | (7.7, 1.7) | |||||||||
5″ | 6.67 d (8.1) | 116.2 | 7.05 t (7.7) | 130.3 | 6.71 | 127.8 | 7.11 | 128.1 | 7.23 | 129.6 |
6″ | 6.97 d | 130.4 | 6.63 | 121.9 | 7.02 dd | 131.2 | 7.10 | 131.1 | 7.15 | 129.4 |
(8.1) | (7.7, 1.7) | |||||||||
1‴ | - | - | - | - | - | - | 4.89 d | 102.7 | 4.30 d | 104.0 |
(7.5) | (7.8) | |||||||||
2‴ | - | - | - | - | - | - | 3.48 m | 75.2 | 3.19 m | 75.5 |
3‴ | - | - | - | - | - | - | 3.40 m | 78.2 | 3.18 m | 77.8 |
4‴ | - | - | - | - | - | - | 3.40 m | 71.6 | 3.32 m | 71.9 |
5‴ | - | - | - | - | - | - | 3.46 m | 78.5 | 3.34 m | 78.4 |
6‴ | - | - | - | - | - | - | 3.69 m | 62.7 | 3.67 m | 63.0 |
3.89 m | 3.89 m | |||||||||
3′-OCH3 | 3.82 s | 56.5 | 3.82 s | 56.5 | 3.82 s | 56.5 | 3.82 s | 56.5 | 3.82 | 56.6 |
Compound | IC50 ± SD (μM) | |||||
---|---|---|---|---|---|---|
A375P | B16F1 | B16F10 | A549 | MCF-7 | HT-29 | |
1 | 14.75 ± 1.00 | 31.73 ± 4.46 | 21.71 ± 3.65 | 26.07 ± 2.08 | 11.50 ± 0.71 | 11.96 ± 0.74 |
2 | 45.52 ± 1.09 | 56.03 ± 0.74 | 59.31 ± 0.42 | 62.92 ± 3.07 | 42.95 ± 0.80 | 54.88 ± 4.16 |
3 | >80 | >80 | >80 | >80 | >80 | >80 |
3a | >80 | >80 | >80 | >80 | >80 | >80 |
3b | >80 | >80 | >80 | >80 | >80 | >80 |
4 | 45.62 ± 0.41 | 22.97 ± 1.94 | 46.13 ± 3.79 | >80 | 60.04 ± 4.97 | >80 |
5 | 29.58 ± 0.45 | 17.84 ± 0.76 | 33.38 ± 2.76 | >80 | 53.66 ± 2.53 | 72.75 ± 2.50 |
6 | 47.91 ± 0.54 | 33.73 ± 2.71 | 46.55 ± 2.15 | >80 | 51.46 ± 1.66 | >80 |
7 | 38.79 ± 1.47 | 29.28 ± 0.76 | 33.58 ± 2.20 | >80 | 34.28 ± 1.76 | >80 |
8 | 75.23 ± 2.89 | 38.37 ± 0.30 | 64.58 ± 3.52 | >80 | 76.34 ± 1.35 | >80 |
9 | 8.36 ± 0.05 | 6.09 ± 0.26 | 9.74 ± 0.20 | >80 | 37.83 ± 1.50 | 35.36 ± 1.17 |
5-FU b | 4.92 ± 0.28 | 5.18 ± 0.78 | 11.22 ± 0.85 | - | - | - |
DZ b | - | - | - | 19.98 ± 0.30 | 8.28 ± 0.13 | 14.98 ± 0.51 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Huo, C.; Han, F.; Xiao, Y.; Kim, H.J.; Lee, I.-S. Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites. Int. J. Mol. Sci. 2022, 23, 3992. https://doi.org/10.3390/ijms23073992
Huo C, Han F, Xiao Y, Kim HJ, Lee I-S. Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites. International Journal of Molecular Sciences. 2022; 23(7):3992. https://doi.org/10.3390/ijms23073992
Chicago/Turabian StyleHuo, Chen, Fubo Han, Yina Xiao, Hyun Jung Kim, and Ik-Soo Lee. 2022. "Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites" International Journal of Molecular Sciences 23, no. 7: 3992. https://doi.org/10.3390/ijms23073992