Abstract
The frequency of human being suffering from cancer is increasing annually throughout the world, but treatment of cancer is becoming more complex in recent years due to the multidrug resistance, creating an urgent demand for novel chemotherapeutics. Betulin and betulinic acid as lupane-type pentacyclic triterpenes distributed ubiquitously in the plant kingdom. Betulin and betulinic acid derivatives could hold the anticancer effects through different mechanisms, inclusive of induction of apoptosis and autophagy, antiangiogenesis, inhibition of invasion and migration, cell cycle arrest and multidrug resistance reversal. Notably, betulin and betulinic acid hybrids have been recently identified as promising candidates to explore novel anticancer chemotherapeutics since these derivatives could circumvent multidrug resistance, reduce the toxicity, and improve the efficacy. This review outlines the research progress regarding the anticancer potential of betulin and betulinic acid hybrids from 2012 to 2022, and the structure–activity relationship and mechanisms of action were also discussed.
REFERENCES
Matthews, H.K., Bertoli, C., and Bruin, R.A.M., Nat. Rev. Mol. Cell Biol., 2022, vol. 23, p. 74. https://doi.org/10.1038/S41580-021-00404-3
Santucci, C., Carioli, G., Bertuccio, P., Malvezzi, M., Pastorino, U., Boffetta, P., Negri, E., Bosetti, C., and Vecchia, C., Eur. J. Cancer Prevent., 2020, vol. 29, p. 367. https://doi.org/10.1097/CEJ.0000000000000594
Siegel, R.L., Miller, K.D., Fuchs, H.E., and Jemal, A., CA Cancer J. Clin., 2022, vol. 72, p. 7. https://doi.org/10.3322/caac.21708
Emran, T.B., Shahriar, A., Mahmud, A.R., Rahman, T., Abir, M.H., Siddiquee, M.F.R., Ahmed, Ho., Islam, A., and Hassan, M.M., Front. Oncol., 2022, vol. 12, e891652. https://doi.org/10.3389/fonc.2022.891652
Behranvand, N., Nasri, F., Emameh, R.Z., Khani, P., Hosseini, A., Garssen, J., and Falak, R., Cancer Immunol. Immunother., 2022, vol. 71, p. 507. https://doi.org/10.1007/s00262-021-03013-3
El-Hussein, A., Manoto, S.L., Ombinda-Lemboumba, S., Alrowaili, Z.A., and Mthunzi-Kufa, P., Anti-Cancer Agents Med. Chem., 2021, vol. 21, p. 149. https://doi.org/10.2174/1871520620666200403144945
Peng, Y., Tang, D., Zhao, M., Kajiyama, H., Kikkawa, F., and Kondo, Y., Cancer Metast. Rev., 2020, vol. 39, p. 825. https://doi.org/10.1007/s10555-020-09910-w
Pu, F., Chen, F., Zhang, Z., Shi, D., Zhong, B., Lv, X., Tucker, A.B., Liu, J., and Shao, Z., Genes Dis., 2022, vol. 9, p. 347. https://doi.org/10.1016/j.gendis.2020.11.019
Sousa, J.L.C., Freire, C.S.R., Silvestre, A.J.D., and Silva, A.M.S., Molecules, 2019, vol. 24, p. e355. https://doi.org/10.3390/molecules24020355
Hordyjewska, A., Ostapiuk, A., Horecka, A., and Kurzepa, J., Phytochem. Rev., 2019, vol. 18, p. 929. https://doi.org/10.1007/s11101-019-09623-1
Lombrea, A., Scurtu, A. D., Avram, S., Pavel, I. Z., Turks, M., Lugiņina, J., Peipiņš, U., Dehelean, C. A., Soica, C., and Danciu, C., Int. J. Mol. Sci., 2021, vol. 22, e3676. https://doi.org/10.3390/ijms22073676
Cháirez-Ramírez, M., Moreno-Jiménez, M., GonzálezLaredo, R., Gallegos-Infante, J., and Rocha-Guzmán, N., EXCLI J., 2016, vol. 15, p. 758. https://doi.org/10.17179/excli2016-642
Zhang, X., Hu, J., and Chen, Y., Mol. Med. Rep., 2016, vol. 14, p. 4489. https://doi.org/10.3892/mmr.2016.5792
Jiang, W., Li, X., Dong, S., and Zhou, W., Biomed. Pharmacother., 2021, vol. 142, e111990. https://doi.org/10.1016/j.biopha.2021.111990
Ali-Seyed, M., Jantan, I., Vijayaraghavan, K., and Bukhari, S.N.A., Chem. Biol. Drug Des., 2016, vol. 87, p. 517. https://doi.org/10.1111/cbdd.12682
Amiri, S., Dastghaib, S., Ahmadi, M., Mehrbod, P., Khadem, F., Behrouj, H., Aghanoori, M.R., Madrakian, T., and Ghavami, S., Biotech. Adv., 2020, vol. 38, p. e107409. https://doi.org/10.1016/j.biotechadv.2019.06.008
Meunier, B., Acc. Chem. Res., 2008, vol. 41, p. 69. https://doi.org/10.1021/ar7000843
Mishra, S.S. and Singh, P., Eur. J. Med. Chem., 2016, vol. 124, p. 500. https://doi.org/10.1016/j.ejmech.2016.08.039
Zhong, Y., Liang, N., Liu, Y., and Cheng, M.S., Chin. J. Nat. Med., 2021, vol. 19, p. 641. https://doi.org/10.1016/S1875-5364(21)60097-3
Zhang, D.M., Xu, H.G., Wang, L., Li, Y.J., Sun, P.H., Wu, X.M., Wang, G.J., Chen, W.M., and Ye, W.C., Med. Res. Rev., 2015, vol. 35, p. 1127. https://doi.org/10.1002/med.21353
Lang, D. K., Kaur, R., Arora, R., Saini, B., and Arora, S., Anti-Cancer Agents Med. Chem., 2020, vol., 20, p. 2150. https://doi.org/10.2174/1871520620666200705214917
Rani, D., Garg, V., and Dutt, R., Anti-Cancer Agents Med. Chem., 2021, vol. 21, p., 1957. https://doi.org/10.2174/1871520621666210112112422
Ahmad, K., Khan, M.K.A., Baig, M.H., Imran, M., and Gupta, G.K., Anti-Cancer Agents Med. Chem., 2018, vol. 18, p. 46. https://doi.org/10.2174/1871520616666161221112042
Jabir, N.R., Firoz, C.K., Bhushan, A., Tabrez, S., and Kamal, M.A., Anti-Cancer Agents Med. Chem., 2018, vol. 18, p. 6. https://doi.org/10.2174/1871520616666160520112839
Sidova, V., Zoufaly, P., Pokorny, J., Dzubak, P., Hajduch, M., Popa, I., and Urban, M., PLoS ONE, 2017, vol. 12, E0171621. https://doi.org/10.1371/journal.pone.0171621
Dangroo, N.A., Singh, J., Rath, S.K., Gupta, N., Qayum, A., Singh, S., and Sangwan, P.L., Steroids, 2017, vol. 123, p. 1. https://doi.org/10.1016/j.steroids.2017.04.002
Khan, I., Guru, S.K., Rath, S.K., Chinthakindi, P.K., Singh, B., Koul, S., Bhushan, S., and Sangwan, P.L., Eur. J. Med. Chem., 2016, vol. 108, p. 104. https://doi.org/10.1016/j.ejmech.2015.11.018
Suman, P., Patel, A., Solano, L., Jampana, G., Gardner, Z.S., Holt, C.M., and Jonnalagadda, S.C., Tetrahedron 2017, vol. 73, p. 4214. https://doi.org/10.1016/j.tet.2016.11.056
Majeed, R., Hamid, A., Sangwan, P.L., Chinthakindi, P.K., Koul, S., Rayees, S., Singh, G., Rath, S.K., and Saxena, A.K., Cell Death and Disease 2014, vol. 50, p. E1459. https://doi.org/10.1038/cddis.2014.387
Majeed, R., Sangwan, P.L., Chinthakindi, P.K., Khan, I., Dangroo, N.A., Thota, N., Hamid, A., Sharma, P.R., Saxena, A.K., and Koul, S., Eur. J. Med. Chem., 2013, vol. 63, p. 782. https://doi.org/10.1016/j.ejmech.2013.03.028
Chakraborty, B., Dutta, D., Mukherjee, S., Das, S., Maiti, N.C., Das, P., and Chowdhury, C., Eur. J. Med. Chem., 2015, vol. 102, p. 93. https://doi.org/10.1016/j.ejmech.2015.07.035
Dutta, D., Chakraborty, B., Sarkar, A., Chowdhury, C., and Das, P., BMC Cancer, 2016, vol. 16, e23. https://doi.org/10.1186/s12885-016-2055-1
Ding, W., Sun, M., Luo, S., Xu, T., Cao, Y., Yan, X., and Wang, Y., Molecules, 2013, vol. 18, p. 10228. https://doi.org/10.3390/molecules180910228
Grishko, V.V., Tolmacheva, I.A., Nebogatikov, V.O., Galaiko, N.V., Nazarov, A.V., Dmitriev, M.V., and Ivshina, I.B., Eur. J. Med. Chem., 2017, vol. 125, p. 629. https://doi.org/10.1016/j.ejmech.2016.09.065
Zhang, H., Zhu, P., Liu, J., Lin, Y., Yao, H., Jiang, J., Ye, W., Wu, X., and Xu, J., Bioorg. Med. Chem. Lett., 2015, vol. 25, p. 728. https://doi.org/10.1016/j.bmcl.2014.11.058
Tang, L., Lv, S.J., Wu, Z., Qian, M., Xu, Y., Gao, X., Wang, T., Xiao, J., Wei, H., Oncol. Lett., 2021, vol. 22, p. e605. https://doi.org/10.3892/ol.2021.12866
Kazakova, O.B., Medvedeva, N.I., Lopatina, T.V., Apryshko, G.N., Pugacheva, R.B., Yavorskaya, N.P., Golubeva, I.S., and Tolstikov, G.A., Russ. J. Bioorg. Chem., 2015, vol. 41, p. 305. https://doi.org/10.1134/S1068162015020065
Khusnutdinova, E.F., Petrova, A.V., Lobov, A.N., Kukovinets, O.S., Baev, D.S., and Kazakova, O.B., Nat. Prod. Res., 2021, vol. 35, p. 3850. https://doi.org/10.1080/14786419.2020.1744139
Zhang, H., Li, F., Zhu, P., Liu, J., Yao, H., Jiang, J., Ye, W., Wu, X., and Xu, J., Chem. Biol. Drug Des., 2015, vol. 86, p. 424. https://doi.org/10.1111/cbdd.12543
Krishna, C., Bhargavi, M.V., and Krupadanam, B.L.D., Russ. J. Gen. Chem., 2018, vol. 88, p. 312. https://doi.org/10.1134/S1070363218020196
Krishna, C., Bhargavi, M.V., and Krupadanam, B.L.D. J. Asian Nat. Prod. Res., 2016, vol. 18, p. 1158. https://doi.org/10.1080/10286020.2016.1196193
Borková, L., Frydrych, I., Jakubcová, N., Adámek, R., Lišková, B., Gurská, S., Medvedíková, M., Hajdúch, M., and Urban, M., Eur. J. Med. Chem., 2020, vol. 185, e111806. https://doi.org/10.1016/j.ejmech.2019.111806
Li, S., and Hu, S.M., Trop. J. Pharm. Res., 2020, vol., 19, p. 957. https://doi.org/10.4314/tjpr.v19i5.7
Shaik, B., Deeb, O., Agrawal, V.K., and Gupta, S.P., Lett. Drug Des. Dis., 2017, vol. 14, p. 83. https://doi.org/10.2174/1570180813999160721160833
Qi, S.Z., Zhang, X.X., Jin, Y., Wang, M., Long, L.P., Jing, W.H., Song, K.R., Wang, D., and Gao, H.Y., Bioorg. Chem., 2021, vol. 111, e104886. https://doi.org/10.1016/j.bioorg.2021.104886
Ren, Y., Anaya-Eugenio, G.D., Czarnecki, A.A., Ninh, T.N., Yuan, C., Chai, H.B., Soejarto, D.D., Burdette, J.E., Blanco, E.J.C., and Kinghorn, A.D. Bioorg. Med. Chem., 2018, vol. 26, p. 4452. https://doi.org/10.1016/j.bmc.2018.07.025
Qi, S.Z., Liu, T., Wang, M., Zhang, X.X., Yang, Y.R., Jing, W.H., Long, L.P., Song, K.R., Jin, Y., and Gao, H.Y., Bioorg. Chem., 2021, vol. 107, e104628. https://doi.org/10.1016/j.bioorg.2021.104628
Gupta, S., Kumar, S., Kushwaha, P.P., Prajapati, K.S., Shuaib, M., Singh, A.K., and Vardhan, P.S. Chem.-Biol. Interact., 2020, vol. 328, e109200. https://doi.org/10.1016/j.cbi.2020.109200
Yu, P., Li, D.D., Ni, J.J., Xia, C.J., Wang, Z.Z., Xiao, W., Ding, G., and Zhao, L.G., Chem. Nat. Compd., 2019, vol. 55, p. 1080. https://doi.org/10.1007/s10600-019-02899-x
Ganaie, B.A., Shahid, M., Rashid, A., Ara, T., Banday, J.A., Malik, F., and Bhat, B.A., Chem. Biodiversity 2021, vol. 18, E2100292. https://doi.org/10.1002/cbdv.202100292
Khusnutdinova, E., Galimova, Z., Lobov, A., Baikova, I., Kazakova, O., Thu, H.N.T., Tuyen, N.V., Serbian, I., and Hoenke, S., Nat. Prod. Res., 2022, vol. 36, p. 5189. https://doi.org/10.1080/14786419.2021.1922904
Tanasova, M., Begoyan, V.V., and Weseliński, Ł.J., Curr. Top. Med. Chem., 2018, vol. 18, p. 467. https://doi.org/10.2174/1568026618666180523110837
Franconetti, A., López, Ó., and Fernandez-Bolanos, J.G. Curr. Med. Chem., 2020, vol. 27, p. 1206. https://doi.org/10.2174/0929867325666180719114150
Eignerova, B., Tichy, M., Krasulova, J., Kvasnica, M., Rarova, L., Christova, R., Urban, M., BednarczykCwynar, B., Hajduch, M., and Sarek, J., Eur. J. Med. Chem., 2017, vol. 140, p. 403. https://doi.org/10.1016/j.ejmech.2017.09.041
Zhang, H., Zhu, P., Liu, J., Yang, X., Xu, S., Yao, H., Jiang, J., Ye, W., Wu, X., and Xu, J., Eur. J. Med. Chem., 2014, vol. 87, p. 159. https://doi.org/10.1016/j.ejmech.2014.09.058
Yamansarov, E.Y., Skvortsov, D.A., Lopukhov, A.V., Kovalev, S.V., Evteev, S.A., Petrov, R.A., Klyachko, N.L., Ivanenkov, Y.A., and Majouga, A.G., Russ. Chem. Bull., 2019, vol. 68, p. 2331. https://doi.org/10.1007/s11172-019-2707-9
Spivak, A.Y., Galimshina, Z.R., Nedopekina, D.A., and Odinokov, V.N. Chem. Nat. Compd., 2018, vol. 54, p. 315. https://doi.org/10.1007/s10600-018-2331-1
Bache, M., Bernhardt, S., Passin, S., Wichmann, H., Hein, A., Zschornak, M., Kappler, M., Taubert, H., Paschke, R., and Vordermark, D., Int. J. Mol. Sci., 2014, vol. 15, p., 19777. https://doi.org/10.3390/ijms151119777
Zaraei, S.O., Abduelkarem, A.R., Anbar, H.S., Kobeissi, S., Mohammad, M., Ossama, A., and ElGamal, M.I. Eur. J. Med. Chem., 2019, vol. 179, p. 257. https://doi.org/10.1016/j.ejmech.2019.06.052
Chen, H., Deng, X., Fang, G., Tang, Z., and Wan, Y., Eur. J. Med. Chem., 2021, vol. 226, e113837 https://doi.org/10.1016/j.ejmech.2021.113837
Bache, M., Eiselt, Y., Funtan, A., Kahnt, M., Paschke, R., Petrenko, M., Serbian, I., Keßler, J., and Pflüger, E., Eur. J. Med. Chem., 2021, vol. 224, e113721. https://doi.org/10.1016/j.ejmech.2021.113721
Bache, M., Münch, C., Güttler, A., Wichmann, H., Theuerkorn, K., Emmerich, D., Paschke, R., and Vordermark, D., Int. J. Mol. Sci., 2015, vol. 16, p. 26249. https://doi.org/10.3390/ijms161125953
Vanchanagiri, K., Emmerich, D., Bruschke, M., Bache, M., Seifert, F., Csuk, R., Vordermark, D., and Paschke, R., Chem-Biol. Interact., 2018, vol. 284, p. 12. https://doi.org/10.1016/j.cbi.2018.02.014
Weber, L.A., Funtan, A., Paschke, R., Delarocque, J., Kalbitz, J., Meißner, J., Feige, K., Kietzmann, M., and Cavalleri, J.M.V., PLoS ONE, 2020, vol. 15, E0241448. https://doi.org/10.1371/journal.pone.0241448
Güttler, A., Eiselt, Y., Funtan, A., Thiel, A., Petrenko, M., Keßler, J., Thondorf, I., Paschke, R., Vordermark, D., and Bache, M., Int. J. Mol. Sci., 2021, vol. 22, e8808. https://doi.org/10.3390/ijms22168808
Wiemann, J., Heller, L., Perl, V., Kluge, R., Ströhl, D., and Csuk, R., Eur. J. Med. Chem., 2015, vol. 106, p. 194. https://doi.org/10.1016/j.ejmech.2015.10.043
Anh, D.T.T., Cuc, D.T., Giang, L.N.T., Hien, N.T., Doan, V.N., Thanh, N.H., Tuyen, N.V., and Kiem, P.V., Nat. Prod. Commun., 2020, vol. 15, p. 1. https://doi.org/10.1177/1934578X20931967
Pal, A., Ganguly, A., Chowdhuri, S., Yousuf, M., Ghosh, A., Barui, A.K., Kotcherlakota, R., Adhikari, S., and Banerjee, R., ACS Med. Chem. Lett., 2015, vol. 6, p. 612. https://doi.org/10.1021/acsmedchemlett.5b00095
Bildziukevich, U., Rárová, L., Šaman, D., and Wimmer, Z., Eur. J. Med. Chem., 2018, vol. 145, p. 41. https://doi.org/10.1016/j.ejmech.2017.12.096
Giniyatullina, G.V., Petrova, A.V., Mustafin, A.G., Zileeva, Z.R., Kuzmina, U.S., Vakhitova, Y.V., and Kazakova, O.B., ChemistrySelect 2021, vol. 6, p. 13253. https://doi.org/10.1002/slct.202101687
Härmä, V., Haavikko, R., Virtanen, J., Ahonen, I., Schukov, H.P., Alakurtti, S., Purev, E., Nees, M., and Oksman-Caldentey, K.M., PLoS ONE, 2015, vol. 10, E0126111. https://doi.org/10.1371/journal.pone.0126111
Giniyatullina, G.V. and Kazakova, O.B., Chem. Nat. Compd., 2021, vol. 57, p. 698. https://doi.org/10.1007/s10600-021-03453-4
Liu, J., Zhu, Z., Tang, J., Lin, Q., Li, C., and Sun, J., Anti-Cancer Agents Med. Chem., 2017, vol. 17, p. 241. https://doi.org/10.2174/1871520616666160926115747
Liu, J.H., Tang, J., Zhu, Z.F., and Chen, L., J. Asian Nat. Prod. Res., 2014, vol. 16, p. 34. https://doi.org/10.1080/10286020.2013.870998
Zhang, L., Hou, S., Li, B., Pan, J., Jiang, L., Zhou, G., Gu, H., Zhao, C., Lu, H., and Ma, F., OncoTargets Ther., 2018, vol. 11, p. 361. https://doi.org/10.2147/OTT.S154412
Tsepaeva, O.V., Nemtarev, A.V., Salikhova, T.I., Abdullin, T. I., Grigoreva, L.R., Khozyainova, S.A., and Mironov, V.F., Anti-Cancer Agents Med. Chem., 2020, vol., 20, p. 286. https://doi.org/10.2174/1871520619666191014153554
Nedopekina, D.A., Gubaidullin, R.R., Odinokov, V.N., Maximchik, P.V., Zhivotovsky, B., Bel’skii, Y.P., Khazanov, V.A., Manuylova, A.V., Gogvadze, V., and Spivak, A.Y., MedChemComm., 2017, vol. 18, p., 1934. https://doi.org/10.1039/C7MD00248C
Spivak, A.Y., Nedopekina, D.A., Khalitova, R.R., Gubaidullin, R.R., Odinokov, V.N., Bel’skii, Y.P., Bel’skaya, N.V., and Khazanov, V.A., Med. Chem. Res., 2017, vol. 26, p. 518. https://doi.org/10.1007/s00044-016-1771-z
Tsepaeva, O.V., Nemtarev, A.V., Abdullin, T.I., Grigor’eva, L.R., Kuznetsova, E.V., Akhmadishina, R.A., Ziganshina, L.E., Cong, H.H., and Mironov, V.F.D., J. Nat. Prod., 2017, vol. 80, p. 2232. https://doi.org/10.1021/acs.jnatprod.7b00105
Kodr, D., Stanková, J., Rumlová, M., Džubák, P., Řehulka, J., Zimmermann, T., Křížová, I., Drašar, P.B., and Jurášek, M., Biomed., 2021, vol. 9, e1104. https://doi.org/10.3390/biomedicines9091104
Yang, S., Liang, N., Li, H., Xue, W., Hu, D., Jin, L., Zhao, Q., and Yang, S., Chem. Cent. J., 2012, vol. 6, e141. https://doi.org/10.1186/1752-153X-6-141
Yang, S.J., Liu, M.C., Zhao, Q., Hu, D.Y., Xue, W., and Yang, S., Eur. J. Med. Chem., 2015, vol. 96, p. 58. https://doi.org/10.1016/j.ejmech.2015.04.006
Cui, H.W., He, Y., Wang, J., Gao, W., Liu, T., Qin, M., Wang, X., Yi, Z., and Qiu, W.W., Eur. J. Med. Chem., 2015, vol. 95, p. 240. https://doi.org/10.1016/j.ejmech.2015.03.048
Lu, L., Zhang, H., Liu, J., Liu, Y., Wang, Y., Xu, S., Zhu, Z., and Xu, J., Eur. J. Med. Chem., 2019, vol. 182, e111659. https://doi.org/10.1016/j.ejmech.2019.111659
Chen, J.J., Patel, A., Sodani, K., Xiao, Z.J., Tiwari, A.K., Zhang, D.M., Li, Y.J., Chen, S.D., and Chen, Z.S., PLoS ONE 2013, vol. 8, E74573. https://doi.org/10.1371/journal.pone.0074573
Haeri, H.H., Hinderberger, D., Hussain, H., Kaluđerović, G.N., Morgan, I., Roos, A.H., Sultani, H.N., and Westermann, B., Int. J. Mol. Sci., 2021, vol. 22, e7125. https://doi.org/10.3390/ijms22137125
Csuk, R., Nitsche, C., Sczepek, R., Schwarz, S., and Siewert, B., Arch. Pharm., 2013, vol. 346, p. 232. https://doi.org/10.1002/ardp.20
Yamansarov, E.Y., Saltykova, I.V., Kovalev, S.V., Petrov, I.A., Shkil, D.O., Seleznev, E.I., Beloglazkina, E.K., and Majouga, A.G., Russ. Chem. Bull., 2019, vol. 68, p. 855. https://doi.org/10.1007/s11172-019-2496-1
Khlebnicova, T.S.; Piven, Y.A., Lakhvich, F.A., Sorokina, I.V., Frolova, T.S., Baev, D.S., and Tolstikova, T.G., Anti-Inflammatory & Anti-Allergy Agents Med. Chem., 2020, vol., 19, p. 254. https://doi.org/10.2174/1871523018666190426152049
Khlebnikova, T.S., Piven, Y.A., Lakhvich, F.A., Frolova, T.S., Sorokina, I.V., and Tolstikova, T.G., Chem. Nat. Compd., 2018, vol. 54, p. 1100. https://doi.org/10.1007/s10600-018-2565-y
Emmerich, D., Vanchanagiri, K., Baratto, L.C., Schmidt, H., Paschke, R., Eur. J. Med. Chem., 2014, vol. 75, p. 460. https://doi.org/10.1016/j.ejmech.2014.01.031
Özdemir, Z., Šaman, D., Rárová, L., Rybková, M., Vlk, M., and Wimmer, Z., Molecules, 2020, vol. 25, e3546. https://doi.org/10.3390/molecules25153546
Ackermann, A., Karagöz, A.Ç., Ghoochani, A., Buchfelder, M., Eyüpoglu, I., Tsogoeva, S.B., and Savaskan, N., Oncotarget, 2017, vol. 8, p. 61457. https://doi.org/10.18632/oncotarget.18390
Couto, N.M.G.D., Willig, J.B., Ruaro, T.C., Oliveira, D.L.D., Buffon, A., Pilger, D.A., Arruda, M.S.P., Miron, D., Zimmer, A.R., and Gnoatto, S.C.B., Anti-Cancer Agents Med. Chem., 2020, vol., 20, 622. https://doi.org/10.2174/1871520620666200124111634
Wolfram, R.K., Fischer, L., Kluge, R., Ströhl, D., Al-Harrasi, A., and Csuk, R., Eur. J. Med. Chem., 2018, vol. 155, p. 869. https://doi.org/10.1016/j.ejmech.2018.06.051
Pattnaik, B., Lakshmi, J.K., Kavitha, R., Jagadeesh, B., Bhattacharjee, D., Jain, N., and Mallavadhani, U.V., J. Asian Nat. Prod. Res., 2017, vol., 19, p. 260. https://doi.org/10.1080/10286020.2016.1240169
Xu, B., Yan, W.Q., Xu, X., Wu, G.R., Zhang, C.Z., Han, Y.T., Chu, F.H., Zhao, R., Wang, P.L., and Lei, H.M., Eur. J. Med. Chem., 2017, vol. 130, p. 26. https://doi.org/10.1016/j.ejmech.2017.02.036
Ngoc, T.D., Moons, N., Kim, Y., Borggraeve, W.D., Mashentseva, A., Andrei, G., Snoeck, R., Balzarini, J., and Dehaen, W., Bioorg. Med. Chem., 2014, vol. 22, p. 3292. https://doi.org/10.1016/j.bmc.2014.04.061
Pokorny, J., Krajcovicova, S., Hajduch, M., Holoubek, M., Gurska, S., Dzubak, P., Volna, T., Popa, I., and Urban, M., Future Med. Chem., 2018, vol. 10, p. 483. https://doi.org/10.4155/fmc-2017-0171
Baratto, L.C., Porsani, M.V., Pimentel, I.C., Netto, A.B.P., Paschke, R., and Oliveira, B.H., Eur. J. Med. Chem., 2013, vol. 68, p. 121. https://doi.org/10.1016/j.ejmech.2013.07.012
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Wang, J., Shi, Ym. Recent Updates on Anticancer Activity of Betulin and Betulinic Acid Hybrids (A Review). Russ J Gen Chem 93, 610–627 (2023). https://doi.org/10.1134/S1070363223030180
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DOI: https://doi.org/10.1134/S1070363223030180