Accepted Manuscript New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti proliferative activity on human cancer cells Le Quynh Lien, Tran My Linh,[.]
Accepted Manuscript New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells Le Quynh Lien, Tran My Linh, Vu Huong Giang, Nguyen Chi Mai, Nguyen Xuan Nhiem, Bui Huu Tai, Nguyen Thị Cuc, Hoang Le Tuan Anh, Ninh Khac Ban, Chau Van Minh, Phan Van Kiem PII: DOI: Reference: S0960-894X(16)30716-8 http://dx.doi.org/10.1016/j.bmcl.2016.07.014 BMCL 24058 To appear in: Bioorganic & Medicinal Chemistry Letters Received Date: Revised Date: Accepted Date: 28 May 2016 July 2016 July 2016 Please cite this article as: Lien, L.Q., Linh, T.M., Giang, V.H., Mai, N.C., Nhiem, N.X., Tai, B.H., Cuc, N.T., Anh, H.L.T., Ban, N.K., Minh, C.V., Kiem, P.V., New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells, Bioorganic & Medicinal Chemistry Letters (2016), doi: http://dx.doi.org/10.1016/j.bmcl.2016.07.014 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain Bioorg Med Chem Lett New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells Le Quynh Lien, Tran My Linh, Vu Huong Giang, Nguyen Chi Mai, Nguyen Xuan Nhiem, Bui Huu Tai, Nguyen Th Cuc, Hoang Le Tuan Anh, Ninh Khac Ban, Chau Van Minh, and Phan Van Kiem* Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam *Corresponding author: Phan Van Kiem, Prof Ph.D Institute of Marine Biochemistry, Vietnam Academy of Science and Technology 18-Hoang Quoc Viet, Caugiay, Hanoi, Vietnam Tel.: +84-4-3791-7053 Fax: +84-4-3791-7054 -1- E-mail: phankiem@yahoo.com ABTRACT Five new compounds, named ancistronaphtosides A and B (1 and 2), anciscochine (3), anciscochine 6-O- -D-glucopyranoside (4), and -methoxy-5-epi-ancistecrorine A1 (5), together with tortoside A (6) and 4-hydroxy-2-methoxyphenyl-6-O-syringoyl- -D-glucopyranoside (7) were isolated from the methanolic extract of Ancistrocladus cochichinensis Their chemical structures were established using HR-ESI-MS, NMR spectroscopic, and chiroptical methods Compound significantly exhibited anti-proliferation against HL-60, LU-1, and SK-MEL-2 cells with IC50 values of 5.0 ± 1.2, 6.5 ± 1.6, and 6.8 ± 2.0 µg/mL, respectively Keyword: Ancistrocladus cochinchinensis, isoquinoline alkaloid, naphthalene derivative, Antiproliferation -2- The genus Ancistrocladus Wall (Ancistrocladaceae family) comprises around 16 species of lianas and distributes in evergreen tropical forests from Africa to southeastern Asia.[1] They are rich in naphtylisoquinoline alkaloids (NIQs) which exhibited unique chemical structure, specific biological activities and hence recently received much interests of medicinal chemists To date, over 140 NIQs have been identified, evaluated their biological effects.[2] Notably, Nmethylancistectorine A1, ancistectorine A2, 5-epi-ancistectorine A2, and jozimine A2 isolated from A tectorius and un-investigated Congolese Ancistrocladus species, exhibiting excellent and selective antiplasmodial activity against Plasmodium falciparum strain (IC50 values of 80.0, 70.0, 30.0, and 1.4 nM, respectively).[3, 4] Dioncophyllines A-C displayed good anti- trypanosomal activity towards Trypanosoma brucei TC221 with the EC50 values as low as of 3.4, 2.6, and 4.2 nmol/mL, respectively.[5] Several NIQs and related analogues have been synthesized to verify and improve bioactivities.[6] A cochinchinensis is an endemic species of Vietnam It has been used in folk medicines with diruric, anti-febrile, and anti-phlogistic properties.[7] A few chemical investigations of A cochinchinensis isolated tetralones,[7] C/C- coupled[8] and N/C-coupled[2] NIQs which were remarked this plant as a promising candidate for researches of new secondary metabolites as well as NIQs In this paper, we describe the isolation, structure elucidation, and antiproliferation towards cancer cells of five new compounds belonging to naphthalene, isoquinonline, and naphtylisoquinoline derivatives that were isolated from A cochinchinensis leaves The plant materials, A cochinchinensis, were collected in March 2013 at Vinh Phuc province, Vietnam and taxonomically identified by one of the authors, Prof Ninh Khac Ban Voucher specimen (TNSV-TQ8) was deposited at the Institute of Marine Biochemistry, VAST, Vietnam Air-dried leaves of A cochinchinensis were ultrasonically extracted with MeOH Concentrated extract was successively partitioned with CH2Cl2 and EtOAc to give corresponding soluble -3- fractions From these fractions, by using combination of various chromatographic procedures, five new secondary metabolites ancistronaphtosides A and B (1 and 2), anciscochine (3), anciscochine 6-O- -D-glucopyranoside (4), and -methoxy-5-epi-ancistecrorine A1 (5), together with two known compounds tortoside A (6) and 4-hydroxy-2-methoxyphenyl-6-O-syringoyl- D-glucopyranoside (7) were separated and purified (See Fig 1, Supporting information) Figure Chemical structures of compounds 1-7 isolated from A cochinchinensis Ancistronaphtoside A (1)[9] was obtained as a white amorphous powder Its molecular formula was deduced to be C22H28O11 by positive-mode HR-ESI-MS (m/z 491.1539 [M+Na]+, calcd for [C22H28O11Na]+, 491.1524) and 13 C-NMR spectroscopic data, indicating nine indices of hydrogen deficiency The 1H NMR spectra of showed characteristic resonances for five aromatic protons [AX system: H 7.32 (1H, br s) and 7.20 (1H, br s); ABC system: H 7.28 (1H, dd, J = 7.5, 7.5 Hz), 7.22 (1H, dd, J = 1.0, 7.5 Hz), and 6.75 (1H, dd, J = 1.0, 7.5 Hz)], two anomeric protons [ group H H 5.09 (1H, d, J = 7.5 Hz) and 5.03 (1H, d, J = 2.0 Hz)], and one methyl 2.47 (3H, s) The 13 C-NMR and DEPT spectra of revealed 22 carbon resonances, -4- comprising one methyl, three methylenes, 12 methines, and six non-protonated carbons (Table 1) Among them, two anomeric carbons ( C 110.9 and 104.5) and nine oxygenated aliphatic carbons ( C 65.7 through 80.6) suggested for the presence of two sugar units Remaining ten sp carbons ( C 110.9 through 155.6) and a methyl carbon ( C 22.0), in conjunction with the rest of seven indices of hydrogen deficiency were assigned for a naphtalene structure.[10] In the HMBC spectrum (Fig 2), methyl proton H 2.47 was found to have strong correlations with C 123.6 (C-1), 137.2 (C-2), and 114.0 (C-3); together with HMBC correlation between proton H-1 ( 7.32) and C H 119.6 (C-8) of ABC system which were indicated the position of methyl group at C-2 Figure Important HMBC correlations of compounds 1, 2, 4, and The HMBC correlations of protons H-6 ( H 6.75)/ H-7 ( H 7.28) with C-5 ( C 154.9) and its downfield carbon chemical shift suggested a hydroxyl group at C-5 Similarly, HMBC correlations of proton H-3 ( H 7.20) and anomeric proton H-1 ( H 5.09) with C-4 ( C 155.6) were indicated for an O-glycosidic linkage at C-4 Finally, the presence of a -D-apiofuranosyl- -5- (1 6)-O- -D-glucopyranosyl disaccharide moiety was confirmed by its 1D-NMR data, HMBC correlation of H-1 ( H 5.03)/C-6 ( C 68.5), acid hydrolysis and followed by GC analysis.[11] Therefore, the chemical structure of was established as a new compound and named as ancistronaphtoside A Compound 2[9] was assigned a molecular formula of C23H32O13 on the basis of the 13C-NMR and positive-mode HR-ESI-MS (m/z 539.1739 [M+Na]+, calcd for [C23H32O13Na]+, 539.1735), showing eight indices of hydrogen deficiency The 1H-, 13 C-NMR, and HSQC spectra of observed resonant signals attributing to two sp2 methines of AX system [ 6.73 (1H, br s); 4.5, 4.5 Hz), C C 120.4 and 116.7, respectively], an oxygenated methine [ 71.4], two anomeric signals [ H C 103.6 and 100.3, respectively], two methylenes [ (m); C 33.6, 26.6, respectively], a methyl group [ C 6.91 (1H, br s) and H 5.00 (1H, dd, J = 4.38 (1H, d, J = 8.0 Hz) and 4.42 (1H, d, J = 7.5 Hz); carbon ( H H H 2.99 (1H, m), 2.54 (1H, m); 2.18 2.33 (3H, s); C 21.7)], and a ketocarbonyl 204.7) The NMR data of (Table 1) showed a close structural resemblance to However, the appearance of a ketocarbonyl carbon and eight indices of hydrogen deficiency of suggested that was a dihydronaphtalenone derivative In the HMBC of 2, proton H-1 ( and anomeric proton H-1 ( H 4.42) correlated with C-8 ( C H 6.91) 71.4), indicating an O-glycosidic linkage at C-8 Ketone functional group located at C-5 which was confirmed by HMBC correlations between protons H-6 ( ( C H 2.99, 2.54), H-7 ( 204.7) Unlike 1, an -D-glucopyranosyl-(1 H 2.18) and ketocarbonyl carbon C-5 6)-O- -D-glucopyranosyl disaccharide moiety was deduced in the structure of from its 1D-NMR data, HMBC correlation of H-1 ( 4.38)/C-6 ( C 68.5), H acid hydrolysis and followed by GC analysis.[11] Absolute configuration at C-8 was determined to be ‘R’ by a positive Cotton effect ( 266 +6.19) observed in the CD spectrum of in contrast with R/S-configurations of similar chromophore structures in the literature (R: 265 +12; S: 263 −4).[12] Consequently, chemical structure of was determined and named as ancistronaphtoside B -6- Table 1: NMR spectroscopic data for compounds 1-4 No C 123.6 137.2 114.0 155.6 154.9 110.9 10 2-Me Glc-1 128.4 119.6 138.4 115.1 22.0 104.5 75.0 78.2 71.5 77.4 68.5 Api/Glc-1 110.9 78.1 80.6 75.1 65.7 1a H (mult., J in Hz) 7.32 (br s) 7.20 (br s) 6.75 (dd, 1.0, 7.5) 7.28 (dd, 7.5, 7.5) 7.22 (dd, 1.0, 7.5) 2.47 (s) 5.09 (d, 7.5) 3.58 (dd, 7.5, 9.0) 3.52 (dd, 9.0, 9.0) 3.43 (dd, 9.0, 9.0) 3.68* 3.68* 4.10 (dd, 3.0, 12.0) 5.03 (d, 2.0) 3.97 (d, 2.0) 3.78 (d, 9.5) 4.00 (d, 9.5) 3.61 (s) C 120.4 148.1 116.7 161.5 204.7 33.6 26.6 71.4 143.8 113.4 21.7 100.3 73.5 76.9 70.3 76.7 68.5 103.6 73.3 76.7 2b H (mult., J in Hz) 6.91 (br s) 6.73 (br s) 2.99 (m) 2.54 (m) 2.18 (m) 5.00 (dd, 4.5, 4.5) 2.33 (s) 4.42 (d, 7.5) 2.99 (m) 3.08 (m) 3.08 (m) 3.08 (m) 4.00 (br d, 10.5) 3.63 (dd, 7.5, 10.5) 4.38 (d, 8.0) 2.99 (m) 3.20 (m) 70.0 3.08 (m) 76.2 61.1 3.44* 3.68 (dd, 4.0, 11.0) 3.44* Measured in a)CD3OD, b)DMSO-d 6, *)Overlapped signals -7- No C 3b H (mult., J in Hz) C 4a H (mult., J in Hz) 155.8 154.2 112.7 100.7 159.3 99.0 7.29 (s) 6.63 (d, 2.0) 6.52 (d, 2.0) 158.9 154.2 116.0 103.3 160.9 100.8 7.55 (s) 7.04 (d, 2.0) 6.84 (d, 2.0) 10 1-Me 3-CH2OH 8-OMe 3-CH2OH 6-OH Glc-1 159.3 140.5 113.7 27.9 63.9 55.7 2.86 (s) 4.54 (s) 3.89 (s) 5.30 (br s) 10.15 (br s) 161.1 142.2 117.0 27.5 65.2 56.3 2.98 (s) 4.74 (s) 4.01 (s) 101.8 74.8 78.3 5.14 (d, 7.5) 3.56 (m) 3.60 (m) 71.4 77.9 62.5 3.44 (dd, 9.0, 9.0) 3.56 (m) 3.97 (dd, 2.5, 12.0) 3.74 (dd, 6.0, 12.0) Compound [9] was obtained as a pale yellow amorphous powder Its molecular formula was determined to be C12H13NO3 from HR-ESI-MS and 13 C-NMR analysis (m/z 220.0969 [M+H]+, calcd for [C12H14NO3]+, 220.0968), indicating seven indices of hydrogen deficiency The HNMR spectrum of displayed signals of three aromatic protons [ H 7.29 (1H, s), 6.63 (1H, d, J = 2.0 Hz), and 6.52 (1H, d, J = 2.0 Hz)], an oxygenated methylene [ methoxy and one methyl group ( H 3.89 and 2.86, each 3H, s) The 13 4.54 (2H, s)], one H C-NMR spectrum of observed signals of 12 carbons which were divided into two methyl, one methylene, three sp methine, and six sp non-protonated carbons by DEPT spectra (Table 1) The aforementioned evidence revealed that is a isoquinoline alkaloid, usually found in Ancitrocladus species.[4, 13] The HMBC correlations between methyl proton ( H 2.86) and carbons C-1 ( 113.7), between oxygenated methylene protons ( H 4.54) and carbons C-3 ( C 155.8)/ C-10 ( C 154.2)/ C-9 ( C C 140.5) were indicated position of methyl and hydroxymethylene group at C-1 and C-3, respectively Due to close in carbon chemical shifts between C-6 ( C 159.3) and C-8 ( C 159.3), the location of methoxy group was further examined by NOESY experiment In the NOESY spectrum, methoxy proton signal ( H 3.89) enhanced by only proton H-7 ( H 3.89) confirming methoxy group at C-8 Consequently, compound was determined to be 6-hydroxy-3hydroxymethyl-1-methyl-8-methoxyisoquinoline and named as anciscochine The 1H- and 13 C-NMR data of compound [9] were identical with those of except for signals belonging sugar moiety (Table 1) The molecular formula of 4, C18H23NO8, was determined by a quasi-molecular ion peak (m/z 382.1499 [M+H]+, calcd for [C18H24NO8]+, 382.1496) in the HR-ESI-MS, indicating an additional of a hexose unit compared with (C12H13NO3) On the other hand, the HMBC correlation between anomeric proton ( C-6 ( C H 5.14) and 160.9) was indicated position of sugar moiety at C-6 Furthermore, acid hydrolysis of obtained D-glucose as confirming by GC analysis and the trace of aglycone was identical with -8- by TLC analysis [Rf 0.27, EtOAc:MeOH:H2O (8/1/0.1, v/v/v,)] Thus, compound was established to be anciscochine 6-O- -D-glucopyranoside Compound [9] was isolated as a pale yellow amorphous powder A C25H29NO4 molecular formula was determined from quasi-molecular ion peak (m/z 408.2160 [M+H]+, calcd for [C25H30NO4]+, 408.2169) in the HR-ESI-MS and the exhibited signals of five aromatic protons [ H 13 C-NMR data The 1H-NMR spectrum of 7.20 (1H, dd, J = 8.0, 8.0 Hz), 6.91 (1H, s), 6.87 (2H, d, J = 8.0 Hz), 6.59 (1H, s)], three methoxy groups ( methyl groups [ H H 3.98, 3.94, 3.61, each 3H, s), three 2.05 (3H, s), 1.78 (3H, d, J = 6.5 Hz), 1.17 (3H, d, J = 6.5 Hz)] (Table 2) Table 2: NMR spectroscopic data for compound in CD3OD The 13 No 51.9 50.5 34.0 10 1-Me 3-Me 8-OMe 10 -Me -OMe -OMe 119.6 156.6 99.2 158.7 115.0 135.4 20.3 19.4 56.0 126.4 136.4 110.5 157.5 158.7 119.2 127.5 107.1 138.2 117.8 20.6 57.0 57.0 C (mult., J in Hz) 4.61 (q, 6.5) 3.16 (m) 2.11 (dd, 6.5, 17.0) 2.16 (dd, 3.5, 17.0) 6.59 (s) 1.78 (d, 6.5) 1.17 (d, 6.5) 3.61 (s) 6.91 (s) 6.87 (d, 8.0) 7.20 (dd, 8.0, 8.0) 6.87 (d, 8.0) 2.05 (s) 3.98 (s) 3.94 (s) H C-NMR spectra of revealed signals of 25 carbons which was classified by DEPT into 11 non-protonated carbons, seven methines, one methylene, and six methyl Among them, -9- signals of 16 carbons was observed in sp region ( C 99.2 through 158.7) The aforementioned NMR data and the presence of a nitrogen atom in the molecular formula of suggested that compound is a naphtylisoquinoline alkaloid, a hybrid structure between naphthalene and isoquinoline derivatives Comparison of the 1H- and 13 C-NMR data of with those of ancistectorine A1,[4] a naphtylisoquinoline alkaloid isolated from A tectorius, showed that both compounds are close in comparable data except for the addition of a methoxy group at C-4 Location of substituted groups in were further re-confirmed by HMBC spectra as shown in the Figure Chemical shifts of C-1 ( C 51.9) and C-3 ( C 50.5) in were suggested both !- orientations of 1-Me and 3-Me groups in comparison with reported !,!-orientations (ancistectorine A1:[4] C 52.1 and 50.9) and ",!-orientations (ancistectorine A2:[4] C 49.6 and 45.3) In addition, the M-helix of biaryl axes in was determined by negative exciton chirality in the CD spectrum (a negative Cotton effect at 244 nm, nm, 230 244 −7.44, and a positive one at 230 +38.64), which was well characterized for naphtylisoquinoline alkaloids.[14] The CD spectrum of was also fully agreed with that of similar structure, 5-epi-ancistectorine A2 ( −16.6, 227 +29.2, 240 −13.6, 284 200 +1.0).[4] Consequently, the structure of was established to be -methoxy-5-epi-ancistecrorine A1 The known compounds tortoside A (6)[15] and 4-hydroxy-2-methoxyphenyl-6-O-syringoyl-D-glucopyranoside (7)[16] were determined since their NMR data was well consisted with previous literature The isolated compounds (1-7) were evaluated their effects on the proliferation of several human cancer cell lines including HL-60 (promyelocytic leukemia cell), LU-1 (lung carcinoma cell), and SK-MEL-2 (melanoma cell) through SRB assay (See Supporting information).[17] Firstly, each compound was screened their effects at a concentration of 20 µg/mL The compound which caused over 50% cell death was subjected for dosedependent study Our results indicated that only compound significantly exhibited cytotoxicity towards tested cancer cells Its IC50 values were 5.0 ± 1.2, 6.5 ± 1.6, and 6.8 ± 2.0 µg/mL - 10 - against HL-60, LU-1, and SK-MEL-2, respectively Ellipticine, a well-known anti-cancer agent, was used as a positive control throughout experiments Others compounds (1-4, 6, 7) were inactivity in our experiment conditions (percentage of cell death lower than 50% at a sample’s concentration of 20 µg/mL) Naphtylisoquinolines are unique chemical structure class, naturally occurring in the small palaeotropical families Dioncophyllaceae and Ancistrocladaceae.[18] They have been demonstrated to exhibit excellent, specific on anti-malarial, anti-protozoal, insecticidal, and anti-HIV activities.[18-20] And hence, they become a great interest of lead compounds for medicinal chemistry.[6] Besides mentioned bioactivities, our results suggested that naphtylisoquinoline, particularly compound 5, is remarkable anti-proliferative activity against HL-60, LU-1, and SK-MEL-2 human cancer cells Further studies to clarify and approve anti-cancer activity of and others naphtylisoquinolines should be done They could be useful as lead compounds for anti-cancer Acknowledgment This research is funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 104.01-2013.53 Supplementary data Supplementary data associated with this article can be found, in the online version, at http:// - 11 - References and Notes Taylor, C M.; Gereau, R E.; Walters, G M Ann Missouri Bot Gard 2005, 92, 360 Bringmann, G.; Hertlein-Amslinger, B.; Kajahn, I.; Dreyer, M.; Brun, R.; Moll, H.; Stich, A.; Ioset, K N.; Schmitz, W.; Ngoc, L H Phytochemistry 2011, 72, 89 Bringmann, G.; Zhang, G.; Büttner, T.; Bauckmann, G.; Kupfer, T.; Braunschweig, H.; Brun, R.; Mudogo, V Chem - A Eur J 2013, 19, 916 Bringmann, G.; Zhang, G.; Ölschläger, T.; Stich, A.; Wu, J.; Chatterjee, M.; Brun, R Phytochemistry 2013, 91, 220 Bringmann, G.; Hoerr, V.; Holzgrabe, U.; Stich, A Pharmazie 2003, 58, 343 Bringmann, G.; Gulder, T.; Hertlein, B.; Hemberger, Y.; Meyer, F J Am Chem Soc 2010, 132, 1151 Anh, N H.; Ripperger, H.; Porzel, A.; Sung, T V.; Adam, G Phytochemistry 1997, 44, 549 Anh, N H.; Porzel, A.; Ripperger, H.; Bringmann, G.; Schäffer, M.; God, R.; Van Sung, T.; Adam, G Phytochemistry 1997, 45, 1287 Physico-chemical properties of new compounds: Compound 1: white amorphous powder; −82.1° (c 0.2, MeOH) HR-ESI-MS m/z: 491.1539 [M+Na]+ (calcd for [C22H28O11Na]+, 491.1524), 469.1706 [M+H]+ (calcd for [C22H29O11]+, 469.1704); 1HNMR (500 MHz) and 13 C-NMR (125 MHz) are given in the Table Compound 2: white −33.6° (c 0.2, MeOH) HR-ESI-MS m/z: 539.1739 [M+Na]+, amorphous powder; calcd for [C23H32O13Na]+, 539.1735; CD (ACN) cm2 mol−1: NMR (500 MHz) and 13 266 +6.19, 214 −28.66; 1H- C-NMR (125 MHz) are given in the Table Compound 3: pale yellow amorphous powder; HR-ESI-MS m/z: 220.0969 [M+H]+ (calcd for [C12H14NO3]+, 220.0968); 1H-NMR (500 MHz) and 13 C-NMR (125 MHz) are given in the Table Compound 4: pale yellow amorphous powder; −58.4° (c 0.2, MeOH); HR-ESI-MS m/z: 382.1499 [M+H]+ (calcd for [C18H24NO8]+, 382.1496); 1H-NMR (500 MHz) and - 12 - 13 C- NMR (125 MHz) are given in the Table Compound 5: pale yellow amorphous powder; −52.7° (c 0.2, MeOH); HR-ESI-MS m/z: 408.2160 [M+H]+ (calcd for [C25H30NO4]+, 408.2169); CD (ACN) cm2 mol−1: 202 −16.47, 230 +38.64, 244 −7.44, 286 +2.85; 1H- NMR (500 MHz) and 13C-NMR (125 MHz) are given in the Table 10 Pathak, A.; Kulshreshtha, D K.; Maurya, R Phytochemistry 2004, 65, 2153 11 Luyen, B T T.; Tai, B H.; Thao, N P.; Yang, S Y.; Cuong, N M.; Kwon, Y I.; Jang, H D.; Kim, Y H Bioorg Med Chem Lett 2014, 24, 4120 12 Bringmann, G.; Münchbach, M.; Messer, K.; Koppler, D.; Michel, M.; Schupp, O.; Wenzel, M.; Louis, A M Phytochemistry 1999, 51, 693 13 Montagnac, A.; Hadi, A H A.; Remy, F.; Païs, M Phytochemistry 1995, 39, 701 14 Bringmann, G.; Gulden, K P.; Holger, B.; Fleischhauer, J.; Kramer, B.; Zobel, E Tetrahedron 1993, 49, 3305 15 Wang, C.; Jia, Z Phytochemistry 1997, 45, 159 16 Hiltunen, E.; Pakkanen Tuula, T.; Alvila, L Holzforschung 2006, 60, 519 17 Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; et al J Natl Cancer Inst 1991, 83, 757 18 Ibrahim, S R M.; Mohamed, G A Fitoterapia 2015, 106, 194 19 Bringmann, G.; Messer, K.; Schwöbel, B.; Brun, R.; Aké Assi, L Phytochemistry 2003, 62, 345 20 Ponte-Sucre, A.; Faber, J H.; Gulder, T.; Kajahn, I.; Pedersen, S E H.; Schultheis, M.; Bringmann, G.; Moll, H Antimicrob Agents Chemother 2007, 51, 188 - 13 - Graphical abstract New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells Le Quynh Lien, Tran My Linh, Vu Huong Giang, Nguyen Chi Mai, Nguyen Xuan Nhiem, Bui Huu Tai, Nguyen Th Cuc, Hoang Le Tuan Anh, Ninh Khac Ban, Chau Van Minh, and Phan Van Kiem* - 14 -