Morphinan Alkaloids from the Leaves of Alphonsea cylindrica and Their Antibacterial Properties

Abstract

A phytochemical study has been carried out on CH₂Cl₂ extract of Alphonsea cylindrica leaves, resulting in the isolation of three new morphinan alkaloids. They are kinomenine (1), N-methylkinomenine (2), and hydroxymethylkinomenine (3). The structures of these compounds were elucidated by extensive spectroscopic analysis (1D and 2D NMR, IR, UV, HRESIMS) and comparison with the data reported in literature for similar alkaloids. Kinomenine (1) and N-methylkinomenine (2) showed weak inhibition against S. aureus (MIC values of 1 and 2 = 500 µg/mL; pIC₅₀ values in 95% C. I. of: 1 = 2.9 to 3.0; 2 = 2.9 to 3.1), while kinomenine (1) also showed weak inhibition against E. coli (MIC values of 1 = 500 µg/mL; pIC₅₀ value in 95% C. I. of: 1 = 2.9) by broth microdilution method. The results obtained can be used as future referencefor the discovery of morphinans and the potential of A. cylindrica as an antibacterial source.

Key words

Annonaceae - Alphonsea cylindrica - morphinan alkaloids - kinomenine - antibacterial properties

Publication History

Received: 12 October 2021

Accepted after revision: 14 March 2022

Accepted Manuscript online:
14 March 2022

Article published online:
06 May 2022

• References

• 1 Talip MA, Azziz SSSA, Wong CF, Awang K, Naz H, Bakri YM, Ahmad MS, Litaudon M. New azafluorenone derivative and antibacterial activities of Alphonsea cylindrica barks. Nat Prod Sc 2017; 23: 151-156
• 2 Wong TM. A Dictionary of Malaysian Timbers. Malaysia: Forest Research Institute Malaysia; 2002
• 3 Aldulaimi AKO, Azziz SSSA, Bakri YM, Nafiah MA, Awang K, Aowda SA, Litaudon M. Two new isoquinoline alkaloids from the bark of Alphonsea cylindrica King and their antioxidant activity. Phytochem Lett 2019; 29: 110-114
• 4 Hanum IF, Ibrahim AZ, Khamis S, Nazre M, Lepun P, Rusea G, Lajuni JJ, Latiff A. An annotated checklist of higher plants in Ayer Hitam forest reserve, Puchong, Selangor. Pertanika J Trop Agric Sci 2001; 24: 63-78
• 5 Turner IM. Annonaceae of the Asia-Pacific region: Names, types and distribution. Gardensʼ Bulletin Singapore 2018; 70: 409-744
• 6 Turner IM. Annonaceae of Malesia: Species Lists for the Floristic Region and some Related Geopolitical Units. 1st ed.. ed. Singapore: Lee Kong Chian Natural History Museum; 2019
• 7 Lúcio ASSC, Almeida JRGS, Da-Cunha EVL, Tavares JF, Filho JMB. Alkaloids of the Annonaceae: Occurrence and a compilation of their biological activities. Alkaloids: Chemistry and Biology 2015; 74: 233-409
• 8 Brummitt RK. Vascular Plant Families and Genera. Kew: Royal Botanic Gardens; 1992: 1
• 9 Andrade NC, Cunha EVL, Silva MS, Agra MF, Barbosa-Filho JM. Terpenoids of the Annonaceae: Distribution and compilation of 13C NMR data. Recent Research Developments in Phytochemistry, Volume 7. Kerala: Research Signpost; 2003: 1-85
• 10 Suman JDSD, Chander A, Surya NS, Padmavathi CH, Madhavi J, Krishna SA. Antioxidant and anticancer activities of an aporphine alkaloid isolated from Alphonsea sclerocarpa . J Phytopharmacol 2018; 7: 51-55
• 11 Thang TD, Huong LT, Dai DN, Ogunwande IA. Essential oil compositions of Alphonsea philastreana (Pierre) Pierre ex Finet & Gagnep. and Alphonsea gaudichaudiana (Baill.) Finet & Gagnep. from Vietnam. Nat Prod Res 2013; 27: 2022-2026
• 12 Hung NV, Dai DN, Thai TH, Thang TD, Ogunwande IA, Ogundajo AL. Essential oil of Alphonsea tonkinensis . Chem Nat Compd 2018; 54: 994-995
• 13 Gopinath KW, Mahanta PK. Polyacetylenverbindungen–237: Über die Polyine aus Alponsea ventricosa Hook F. und Th. Tetrahedron 1976; 32: 737-740
• 14 Jalil J, The CH, Hussain K, Jamal JA, Mohamad HF, Muhammad K. Steroids from Alphonsea curtisii King. propelling science and technology through natural products. Abstract of the International Conference on Natural Products (ICNP 2015), 2015, 154.
• 15 Nandyala VNASR, Chandrasekhar KB. Pharmacognostical standardization & phytochemical evaluation of Alphonsea sclerocarpa Thwaites bark & leaves. Pharmacog J 2017; 9: 196-200
• 16 Weerasinghe A, Puvanendran S, Wickramasinghe A, Karunaratne DN, Wijesundara S, Karunaratne V. Potent bioactivities of the endemic annonaceae heighten its dire conservation status. J Natl Sci Found 2013; 41: 345-350
• 17 Johnson TA, Sohn J, Ward AE, Cohen TL, Lorig-Roach ND, Chen H, Pilli RA, Widjaja EA, Hanafi M, Kardono LBS, Lotulung PD, Boundy-Mills K, Bjeldanes LF. (+)-Altholactone exhibits broad spectrum immune modulating activity by inhibiting the activation of pro-inflammatory cytokines in RAW 264.7 cell lines. Bioorg Med Chem 2013; 21: 4358-4364
• 18 Bakri YM, Aldulaimi AKO, Azziz SSSA, Nafiah MA, Aowda SA, Hazim M, Awang K, Hashim YZH, Abbas P. Cytotoxic and xanthine oxidase inhibitory activities of chemical constituents of Alphonsea Cylindrica King. Res J Pharm Technol 2019; 12: 4129-4134
• 19 Wang XL, Liu BR, Wang JR, Chen CK, Qin GW, Lee SS. Two new morphinane alkaloids from Sinomenium acutum . J Asian Nat Prod Res 2011; 13: 523-528
• 20 Carraz M, Jossang A, Rasoanaivo P, Mazier D, Frappier F. Isolation and antimalarial activity of new morphinan alkaloids on Plasmodium yoelii liver stage. Bioorg Med Chem 2008; 16: 6186-6192
• 21 Lee JY, Kim KJ, Kim J, Choi SU, Kim SH, Ryu SY. Anti-osteoclastogenic effects of isoquinoline alkaloids from the rhizome extract of Sinomenium acutum . Arch Pharm Res 2016; 39: 713-720
• 22 Kashiwaba N, Morooka S, Kimura M, Ono M, Toda J, Suzuki H, Sano T. New morphinane and hasubanane alakloids from Stephania cepharantha . J Nat Prod 1996; 59: 476-480
• 23 Carraz M, Jossang A, Franetich JF, Siau A, Ciceron L, Hannoun L, Sauerwein R, Frappier F, Rasoanaivo P, Snounou G, Mazier D. A plant-derived morphinan as a novel lead compound active against malaria liver stages. PLoS Med 2006; 3: e513
• 24 Zheng X, Zhu W, Han L, Zhang K, Pan T. Highly stereoselective synthesis of functionalised sinomenine derivatives by reducing the C-6 (ring C). J Chem Res 2014; 38: 734-736
• 25 Qader MM, Hamed AA, Soldatou S, Abdelraof M, Elawady ME, Hassane ASI, Belbahri L, Ebel R, Rateb ME. Antimicrobial and antibiofilm activities of the fungal metabolites isolated from the marine endophytes Epicoccum nigrum M13 and Alternaria alternate 13A. Mar Drugs 2021; 19: 232
• 26 Gale EF. Effects of diacetylmorphine and related morphinans on some biochemical activities of Staphylococcus aureus . Mol Pharmacol 1970; 6: 128-133
• 27 Boquet PL, Devynck MA, Aurelle H, Fromageot P. On the bactericidal action of levallorphan–Irreversible alterations of the plasmic membrane. European J Biochem 1971; 21: 536-541
• 28 Clinical and Laboratory Standards Institute (CLSI). M02-A11. Performance standards for antimicrobial disk susceptibility tests: Approved standard–Eleventh edition. Wayne: Clinical and Laboratory Standards Institute; 2012. PA. 19087
• 29 Brito RC, Silva GN, Farias TC, Ferreira PB, Ferreita SB. Standardization of the safety level of the use of DMSO in viability assays in bacterial cells. MOL2NET 2017; 3: 1-6