Three New Pyridine Alkaloids from Vinca major Cultivated in Pakistan

Natural Products and Bioprospecting, Jun 2017

Three new pyridine type alkaloids, (−)-vinmajpyridines A–C (1–3), along with two known alkaloids, have been isolated from the aerial parts of Vinca major cultivated in Pakistan. Their structures have been elucidated by means of NMR and HRESIMS spectroscopic data. The new alkaloids were evaluated for their cytotoxicity against glioma initiating cell lines (GITC-3# and GITC-18#), glioblastoma cell lines (U-87MG and T98G), and lung cancer cell line A-549, but none of them was active at 20 μg/mL concentration.

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Three New Pyridine Alkaloids from Vinca major Cultivated in Pakistan

Nat. Prod. Bioprospect. Three New Pyridine Alkaloids from Vinca major Cultivated in Pakistan Yi-Fen Wang . Xiao-Dong Luo 0 1 2 3 4 5 Xin Wei . Afsar Khan . Da Song . Zhi Dai . 0 1 2 3 4 5 Ya-Ping Liu . Hao-Fei Yu . Bei Wang . 0 1 2 3 4 5 Pei-Feng Zhu . Cai-Feng Ding . Xu-Dong Zhao . 0 1 2 3 4 5 0 D. Song Yunnan College of Business Management , Kunming 650106 , People's Republic of China 1 A. Khan Department of Chemistry, COMSATS Institute of Information Technology , Abbottabad 22060 , Pakistan 2 Z. Dai X.-D. Zhao Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology , Kunming 650223, Yunnan , People's Republic of China 3 X. Wei A. Khan Y.-P. Liu H.-F. Yu B. Wang P.-F. Zhu C.-F. Ding Y.-F. Wang (&) X.-D. Luo (&) State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201 , People's Republic of China 4 X. Wei Y.-P. Liu H.-F. Yu B. Wang P.-F. Zhu C.-F. Ding Y.-F. Wang X.-D. Luo Yunnan Key Laboratory of Natural Medicinal Chemistry , Kunming 650201 , People's Republic of China 5 X. Wei Z. Dai H.-F. Yu B. Wang P.-F. Zhu C.-F. Ding University of Chinese Academy of Sciences , Beijing 100049 , People's Republic of China Three new pyridine type alkaloids, (-)-vinmajpyridines A-C (1-3), along with two known alkaloids, have been isolated from the aerial parts of Vinca major cultivated in Pakistan. Their structures have been elucidated by means of NMR and HRESIMS spectroscopic data. The new alkaloids were evaluated for their cytotoxicity against glioma initiating cell lines (GITC-3# and GITC-18#), glioblastoma cell lines (U-87MG and T98G), and lung cancer cell line A-549, but none of them was active at 20 lg/mL concentration. Vinca major; Apocynaceae; Pyridine alkaloids; Cytotoxicity 1 Introduction The genus Vinca (Apocynaceae), distributed through Europe, Northwest Africa, and South-west Asia, represents a Electronic supplementary material The online version of this article (doi:10.1007/s13659-017-0137-7) contains supplementary material, which is available to authorized users. Xin Wei and Afsar Khan have contributed equally to this work. group of species which are rich in indole alkaloids of diverse structural patterns, many of which are of considerable therapeutic value [ 1?4 ]. Vinca major has been used for centuries as a folk remedy in the treatment of menorrhagia and diabetes, and as an abortifacient and vulnerary [5]. Delphinidin glycosides have been isolated from the flowers of V. major [ 6 ] while chlorogenic acid, robinin, and flavonol triglycoside are extracted from its leaves [ 7 ]. In addition, a number of indole alkaloids are also reported from this plant [ 8?13 ]. Previously, we isolated non-alkaloid constituents [14] as well as indole alkaloids [ 15 ] from V. major cultivated in Kunming. In our ongoing search for alkaloids from this plant growing in different habitats, we carried out the phytochemical investigation of the aerial parts of V. major in Pakistan, and then isolated three new pyridine alkaloids, named as (?)-vincapyridines A?C (1?3) trivially (Fig. 1). The structures of new alkaloids were elucidated by means of spectroscopic methods. The new alkaloids were evaluated for their cytotoxicity against human glioma initiating cell lines (GITC-3# and GITC18#), glioblastoma cell lines (U-87MG and T98G), and lung cancer cell line A-549 using the reported MTS assay with DMSO as the control group. Unfortunately, none of these compounds exhibited significant cytotoxicity at 20 lg/mL concentration. Herein, we report the isolation, structural elucidation of these compounds. 2 Results and Discussion The molecular formula of 1 was determined to be C13H17NO4, by a quasi-molecular ion peak at m/z 252.1222 [M?H]? (calcd for C13H18NO4, 252.1230) in the positive HRESIMS. Its IR spectrum revealed a characteristic absorption band at 1724 (C=O). The 1H and 13C NMR spectral data of 1 (Table 1), assumed that 1 was a trisubstituents pyridine derivative with two typical downfield protons [dH 8.89 (s) and 8.53 (s)] assigned to be pyridine aromatic protons [ 16 ]. In HMBC spectrum of 1, correlations of pyridine protons dC 8.53 (s) with substituents aromatic carbons at dC 146.3 (C-7), 137.6 (C-2), and oxymethine at dC 71.3 (C-3), indicated substituents pattern (Fig. 2). Moreover, HMBC correlations of dH 4.88 (H-5) with dC 71.3 (C-3) and dC 146.3 (C-7) established a substituents pyranose ring fused to the pyridine ring (Fig. 2). Besides, HMBC correlations of dH 1.64 (3H, d, ?CH3) with dC 71.3 (C-3), and of dH 3.99 and 3.62 (2H, ?OCH2CH3) with dC 99.6 (C-5), placed a methyl at C-6 and oxyethyl group at C-5, respectively, which was further supported by the correlations of dH 3.37/4.88, 3.99/1.24, and 5.02/1.64, in its 1H?1H COSY spectrum (Fig. 2). Finally, the HMBC correlations of dH 8.89 (s) and 3.92 (?OCH3) with dC 167.2 (?COOCH3) posit (...truncated)


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Xin Wei, Afsar Khan, Da Song, Zhi Dai, Ya-Ping Liu, Hao-Fei Yu, Bei Wang, Pei-Feng Zhu, Cai-Feng Ding, Xu-Dong Zhao, Yi-Fen Wang, Xiao-Dong Luo. Three New Pyridine Alkaloids from Vinca major Cultivated in Pakistan, Natural Products and Bioprospecting, 2017, pp. 323-327, Volume 7, Issue 4, DOI: 10.1007/s13659-017-0137-7