Table 6.
Anticancer/cytotoxicityactivities ofalkaloids that were obtained from non-Annona genera.
| Alkaloid | Plants | Part of Plant | Country | Anticancer Activity | Ref(s) |
|---|---|---|---|---|---|
| (−)-Anonaine 8 | Nelumbo nucifera Gaertn (Nelumbonaceae) | Leaves | Taiwan | Anti-proliferative effects with IC50 > 500 µM against AGS and 150.1 ± 0.3 µM against DU-145 | [99] |
| Michelia alba D.C. (Magnoliaceae) | Leaves | Taiwan | Inhibited viability of HeLa cancer cells (23 ± 1%) more effectively than non-cancer cells (Vero and MDCK cells, 75 ± 3% and 95 ± 4%, respectively) at concentration of 100 µM. | [100] | |
| Annomontine 53 | Acanthostrongylophora ingens (Petrosiidae) | Sponges | Indonesia | Pronounced cytotoxicity against L5178Y cell line with ED50 7.8 µg/mL compared to the positive control kahalalide F (ED50 6.3 μg/mL) | [97] |
| Acanthostrongylophora ingens (Petrosiidae) | Sponges | Indonesia | Pronounced cytotoxicity against L5178Y cell line with EC50 0.49 µg/mL | [101] | |
| Artabonatine B 23 | Artabotrys hexapetalus (L.f.) Bhandari (Annonaceae) | Roots, stems, and leaves | Taiwan | Active against both Hep G2 and 2,2,15 cell lines with IC50 9.1 and 11.0 µg/mL, respectively | [102] |
| (−)-Asimilobine 9 | Nelumbo nucifera Gaertn (Nelumbonaceae) | Leaves | Taiwan | Anti-proliferative effects against AGS and DU-145 cell lines with IC50 > 500 µM | [99] |
| Cleistopholine 1 | Cananga odorata (Lam.) Hook.f. & Thomson (Annonaceae) | Fruits | Taiwan | Displayed potent cytotoxicity against Hep G2 (human hepatoma cell) and Hep 2,2,15 (Hep G2 cell line transfected with hepatitis B virus) cell lines with IC50 value of 0.22 µg/mL and 0.54 µg/mL, respectively | [103] |
| Disepalum pulchrum (King) J.Sinclair (Enicosanthellum pulchrum, Annonaceae) | Roots | Malaysia | Active against CAOV-3 and SKOV-3 with IC50 value of 61.4 μM and 67.3 μM, respectively. This was comparable with that of the positive control cisplatin (62.8 μM and 67.1 μM) at 24 h of treatment. Cleistopholine (1) at >200 μM showed less cytotoxic effect against normal ovarian cells (SV40). | [104] | |
| Saprosma hainanense Merr. (Rubiaceae) | Stems | China | Inactive against against BEL-7402, SGC-7901, and K-562 cell lines | [105] | |
| (−)-Corydine 29 | Dicranostigma leptopodum (Maxim.) Fedde (Papaveraceae) | Whole plant | China | Showed its cytotoxicity against H1299, MCF-7, and SMCC-7721 with IC50 > 100 µM | [106] |
| Stephania dinklagei (Engl.) Diels (Menispermaceae) | Aerial parts | Ghana | Exhibited cytotoxic activity against KB cell line with IC50 733 μM | [107] | |
| (−)-Corydine 29 | Stephania dinklagei (Engl.) Diels (Menispermaceae) | Stem | Ghana | (−)-Corydine 29 showed DNA-damaging activity in the yeast bioassay (IC50 values YCp50 gal, pRAD52 GAL, Prad52 GLU were27.5, >73.9, and 22.5 μg/mL, respectively | [108] |
| Stephania kwangsiensis H.S. Lo. (Menispermaceae) | Root | India | Three different concentrations (20, 10, 5 µg/mL) could all significantly increase the apoptosis rate (8.77%, 9.12%, and 12.38%, respectively) of NCI-H446 cells after 48 h of treatment compared to the control group (1.02%). (−)-Corydine 29 can inhibit the proliferation of lung cancer NCI-H446 cells and induce their apoptosis | [109] | |
| Corytuberine 16 | Dicranostigma leptopodum (Maxim.) Fedde (Papaveraceae) | Whole plant | China | Cytotoxicity against H1299, MCF-7, and SMCC-7721 with IC50 value of 53.58 ± 5.47 µM, 72.30 ± 1.72 µM, and 73.22 ± 2.35 µM, respectively | [106] |
| Demethylsonodione 79 | Hernandia nymphaefolia (Presi) Kubitzk (Hernandiaceae) | Trunk bark | Taiwan | Exhibited cytotoxic activity against P-388, KB16, A549 (human lung adenocarcinoma), and HT-29 (human colon carcinoma cell lines with ED50 value of 0.766, 0.507, 0.223, and 0.772 µg/mL | [110] |
| Dielsiquinone 3 | Goniothalamus tamirensis Pierre ex Finet & Gagnep. (Annonaceae) | Stem bark | Thailand | Showed cytotoxic activity against A549, HT029, MCF7, RPMI and U251 with ED50 value of 0.11, 1.12, 0.11, 0.11 and 0.37 µM, respectively | [111] |
| Glaucine 68 | Cassytha filiformis L. (Lauraceae) | Whole plant | Benin | Active compound against HeLa cell line with IC50 value of 8.2 µM | [112] |
| Codiaeum variegatum (L.) Rumph. ex A.Juss. (Euphorbiaceae) | Leaves | Egypt | Showed cytotoxic activity against HepG2, MCF7, HCT116, and A549 cell lines with % of inhibition of cell viability of 38.4%, 46.3%, 66.8%, and 17.3%, respectively (at concentration of 100 µg/mL) | [113] | |
| Corydalis turtschaninovii Bess. (Papaveraceae) | Tuber | Korea | Showed cytotoxic activity against A549, SK-OV-3, SK-MEL-2 and HCT-15 cell lines with IC50 value of 26.76 ± 3.82, 21.57 ± 1.01, 20.39 ± 1.45 and 18.63 ± 4.15 µM, respectively | [114] | |
| Isocoreximine 39 | Guatteria blepharophylla Mart (Annonaceae) | Bark | Brazil | Showed anti-proliferative activity against UACC-62, MCF-7, NCI-H460, OVCAR-03, PC-3, HT-29, alagnd 786-0 with TGI value of >764.52 µM, and NCI-ADR/RES (TGI 131.50 µM). This compound showed selective activity for ovarian expressing phenotype for multiple drug resistance (NCI-ADR/RES) with a TGI value of 131.50 µM, but was less active than doxorubicin (TGI value of 14.80 µM) | [98] |
| (+)-Isocorydine 74 | Cassytha filiformis L. (Lauraceae) | Whole plant | Benin | Inactive against HeLa cell with IC50 > 80 µM | [112] |
| Papaver rhoeas L. Papaver rhopalothece Stapf, Papaver macrostomum Boiss. & A.Huet (Papaveraceae) | Aerial parts | Turkey | Nontoxic against normal Vero cell with IC50 value of >300 μg/mL | [115] | |
| Lanuginosine 10 | Magnolia grandiflora L. (Magnoliaceae) | Leaves | Egypt | Exhibited cytotoxicity against U251 and HEPG2 with IC50 value of 4 μg/mL and 2.5 μg/mL, respectively. Lanuginosine 10 was found to be inactive against the HeLa cancer cell. | [116] |
| Liriodenine 11 | Anomianthus dulcis (Dunal) J. Sinclair (Annonaceae) | Stem bark | Thailand | Exhibit the growth of NCIH187, BC, and KB cell lines with IC50 values at 1.02, 13.45 and 14.57 µg/mL, respectively | [117] |
| Broussonetia papyrifera (L.) L′Hér. ex Vent. (Moraceae) | Fruits | China | Exhibit strong cytotoxic effect against A375, BEL-7402, and HeLa cell lines with IC50 value of 5.38 ± 0.27, 6.61 ± 0.57, and 5.97 ± 0.39 µg/mL, respectively | [118] | |
| Cananga odorata (Lam.) Hook.f. & Thomson (Annonaceae) | Stem bark | Bangladesh | Show cytotoxic activity based on brine shrimp method with LC50 value of 4.89 μg/mL | [119] | |
| Cyathostemma argenteum Wild & R.B.Drumm (Vitaceae) | Roots | Malaysia | Found to be similarly and moderately cytotoxic against MCF-7 ADR MDA-MB435 and MT-1 cells lines with IC50 values of 15.6, 16.7, 6.4 and 18.2 µM, respectively | [120] | |
| Disepalum plagioneurum (Diels) D.M.Johnson (Syn Polyalthia plagioneura Diels, Annonaceae) | Stem | China | Cytotoxic activity against GSC-7901, K562, and SPCA-1 cell lines with IC50 value of of 3.87, 37.61, and 6.19 µM, respectively | [121] | |
| Disepalum pulchrum (King) J.Sinclair (syn Enicosanthellum pulchrum (King) Heusden, Annonaceae) | Root | Malaysia | Inhibited CAOV-3 cell growth with IC50 value of.3 ± 1.06 µM after 24 h of exposure. Exhibited less activity against SKOV-3 cells, with IC50 values of 68.0 ± 1.56 µM. | [122] | |
| Goniothalamus gitingensis Elmer (Annonaceae) | Leaves | Philippines | Effective antiproliferative effects against HUVEC and K-562 cell lines with GI50 value of 8.2 ± 0.3 and 6.1 ± 0.8, respectively. | [123] | |
| Liriodenine 11 | Guatteria aberrans Erkens & Maas (Syn Guatteria f riesiana (W.A. Rodrigues) Erkens & Maas, Annonaceae) | Stem bark | Brazil | Anticancer potent against B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), HL-60 (human promyelocytic leukemia), and K562 (human chronic myelocytic leukemia) tumor cell lines with IC50 values of >10, 8.3, 5.5, and 5.0 μM for the respectively | [124] |
| Guatteria blepharophylla Mart. (Annonaceae) | Bark | Brazil | Showed anti-proliferative activity against UACC-62, MCF-7, NCI-H460, OVCAR-03, PC-3, HT-29, 786-0 and NCI-ADR/RES with TGI value of 63.02, 37.67, 87.41, 372.18, >909.09, >909.09, >909.09 and >909.09 µM, respectively. This compound undermined positive control doxorubicin against MCF-7 with TGI value of 46.04 µM. | [98] | |
| Magnolia duperreana Pierre (Syn Kmeria duperreana (Pierre) Dandy, Magnoliaceae) | Stem bark | Thailand | Found to be active against KB and P388 cell lines with ED50 value of of 1.7 and 0.8 µg/mL, respectively | [125] | |
| Magnolia floribunda (Finet & Gagnep.) Figlar (Syn Michelia floribunda Finet & Gagnep., Magnoliaceae) | Stem bark | Thailand | Indicated cytotoxic activity against KB and P388 cell lines with with ED50 value of <2.5 µg/mL | [126] | |
| Michelia compressa var. formosana (Magnoliaceae) | Heartwood | Taiwan | Exhibited powerful inhibitory activity against TW01, H226, Jurkat, A498, A549, and HT1080 carcinoma cell lines with IC50 value of were 8.99, 14.71, 15.7, 4.52, 8.82 and 9.75 μM, respectively | [127] | |
| Michelia compressa var. lanyuensis (Magnoliaceae) | Roots | Taiwan | Possessed cytotoxicity against B16F10 cells after 24 h treatment at high concentration (100 μM) with 80% of cell viability. | [128] | |
| Microcos paniculata L. (Malvaceae) | Branche | Vitenam | Showed low activity against HT-29 cancer cell line with IC50 values greater than 10 μM. | [129] | |
| Miliusa sinensis Finet & Gagnep. (Annonaceae) | Leaves and branches | Vietnam | Indicated a good activity against MCF-7, KB, LU and Hep-G2 cancer cell lines with IC50 value of 2.89, 2.30, 6.66 and 5.23 μg/mL, respectively | [130] | |
| Nelumbo nucifera Gaertn (Nelumbonaceae) | Leaves | Taiwan | Showed anti-proliferative effects against AGS and DU-145 cell lines with IC50 value of >500 and 95.4 ± 0.4 µM, respectively | [99] | |
| Polyalthia longifolia var. pendula (Annonaceae) | Bark | Taiwan | Showed activity against MCF-7 (breast cancer) and MDA-MB-231 cell line with IC50 value of 4.46 and 10.28 µg/mL, respectively | [131] | |
| Liriodenine 11 | Pseuduvaria setosa (King) J. Sinclair (Annonaceae) | Aerial part | Thailand | Strongly cytotoxic to KB and BC cell lines with IC50 2.4 µg/mL and 2.3 µg/mL, respectively | [132] |
| Saprosma hainanense Merr. (Rubiaceae) | Stems | China | Exhibit cytotoxic activities against BEL-7402, SGC-7901, and K-562 cell lines with IC50 value of 71.7, 33.7, and 197.7 µM, respectively | [105] | |
| Stephania dinklagei (Engl.) Diels (Menispermaceae) | Aerial parts | Ghana | Exhibit cytotoxic activity against KB cell line with IC50 value of 26.9 ± 2.4 μM | [107] | |
| Stephania dinklagei (Engl.) Diels (Menispermaceae) | Stem | Ghana | Showed DNA-damaging activity in the yeast bioassay against YCp50 gal, pRAD52 GAL, Prad52 GLU with IC50 value of 0.6, 1.5, and 0.5 μg/mL, respectively. | [108] | |
| Unonopsis guatterioides (A.DC.) R.E.Fr.(Sin Unonopsis buchtienii R. E.Fries, Annonaceae) | Stem | Bolivia | Possessed cytotoxic bioactivity against Vero cell line with IC50 value of 1 μg/mL | [133] | |
| Zanthoxylum nitidum (Roxb.) DC. (Rutaceae) | Stem bark | China | Exhibit cytotoxicity against three human cancer cell lines HT29, A549 and MDA-MB-231 with IC50 values of 9.12, 6.05, and 11.35 μM, respectively | [134] | |
| Zanthoxylum nitidum (Roxb.) DC. (Rutaceae) | Stem bark | Taiwan | Exhibit moderate cytotoxicity against MCF-7, NCI-H460, and SF-268 cancer cell lines with IC50 values of 3.19, 2.38, and 2.19, respectively. Liriodenine (11) was the most cytotoxic isolate in Zanthoxylum nitidum | [135] | |
| (+)-Nornuciferine 73 | Guatteria blepharophylla Mart (Annonaceae) | Stem bark | Brazil | Anti-proliferative activity against MCF-7 NCI-H460 PC-3 HT-29786-0 K562 and NCI-ADR/RES with TGI value of 215.58, 201.99, 542.38, 191.38, 615.23, 153.88 and 255.37 µM, respectively. | [98] |
| Nelumbo nucifera Gaertn (Nelumbonaceae) | Leaves | Taiwan | Anti-proliferative effects against AGS and DU-145 cell lines with IC50 value of >500 µM | [99] | |
| Phoebe grandis (Nees) Merr. (Lauraceae) | Leaves | Malaysia | Cytotoxic activity against NIH/3T3, HeLa and HL-60 with CD50 value of 17, 15 and 37 µg/mL, respectively. | [136] | |
| (+)-Reticuline 19 | Argemone Mexicana L. (Papaveraceae) | Whole plant | Taiwan | Cytotoxic effects against HONE-1 (96% of control) and NUGC (90% of control) at concentration of 150 µM | [137] |
| Dehaasia longipedicellata (Ridl.) Kosterm. (Lauraceae) | Stem bark | Malaysia | Cytotoxicity activities against A549 (IC50 > 200 µg/mL), A375 (IC50 97.600 µg/mL), and BxPC-3 (IC50 82.570 µg/mL) | [138] | |
| Hernandia nymphaefolia (Presi) Kubitzk (Hernandiaceae) | Trunk bark | Taiwan | Anticancer activity against P-388, KB16, A549 (human lung adenocarcinoma), and HT-29 (human colon carcinoma cell lines with ED50 > 50 µg/mL | [139] | |
| Roemerine 49 | Nelumbo nucifera Gaertn (Nelumbonaceae) | Leaves | Taiwan | Showed anti-proliferative effects against AGS and DU-145with IC50 value of >500 and 95.4 ± 0.4 µM, respectively | [99] |
| (−)-Stepholidine 20 | Polyalthia longifolia (Sonn.) Thwaites (Annonaceae) | Bark | Taiwan | Activity against MCF-7 (breast cancer) cell line with IC50 value of 16.56 µg/mL | [131] |
| Squamolone 82 | Artabotrys hexapetalus (L.f.) Bhandari (Syn Artabotrys uncinatus (Lam) Merr., Annonaceae) | Roots, stems, and leaves | Taiwan | Showed significant activity against Hep G2 and 2,2,15 cell lines with IC50 value of 2.8 and 1.6 µg/mL, respectively | [102] |