In vitro antiproliferative activity of alkaloids isolated from Tabernaemontana catharinensis A.DC (Apocynaceae)

Abstract In this work, four alkaloids from the stem bark of T. catharinensis were isolated, namely: voacangine (1); ethyl apovincaminate (2); affinisine (3) and voachalotine (4). The alkaloids were tested in vitro for antiproliferative capacity in eight tumor cell lines: U251 (glioma), MCF-7 (breast), NCI-ADR/RES (drug resistant ovary), 786-0 (kidney), NCI-H460 (lung), HT-29 (colon), K562 (leukemia) and PC-3 (prostate) and a non-tumor keratinocyte cell line (HaCat). Antiproliferative activity was observed after 48 hours and results expressed as the concentration needed to induce 50% growth inhibition (GI50) in µM. The chemotherapy drug Doxorubicin was used as a standard. The alkaloid affinisine (3) was the most promising, showing moderate inhibition rates in addition to the cytotoxic and cytocidal effect against all strains tested. It also proved to be a very promising compound, showing high selectivity rates when compared to the non-tumor keratinocyte cell line (HaCat). Graphical Abstract

[1]  Y. Naidoo,et al.  Major Bioactive Alkaloids and Biological Activities of Tabernaemontana Species (Apocynaceae) , 2021, Plants.

[2]  D. Kawano,et al.  In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts , 2020, Molecules.

[3]  Zhi Xu,et al.  Indole alkaloids with potential anticancer activity. , 2020, Current topics in medicinal chemistry.

[4]  David J Newman,et al.  Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. , 2020, Journal of natural products.

[5]  E. Sauter Cancer prevention and treatment using combination therapy with natural compounds , 2020, Expert review of clinical pharmacology.

[6]  G. Lippi,et al.  Current Cancer Epidemiology , 2019, Journal of epidemiology and global health.

[7]  E. Calvo,et al.  Early Phase clinical drug development of novel agents: a changing paradigm. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  T. Collares,et al.  Extraction, isolation and in vitro evaluation of affinisine from Tabernaemontana catharinensis in human melanoma cells. , 2019, Bioorganic chemistry.

[9]  M. Roesch-Ely,et al.  Bio-guided search of active indole alkaloids from Tabernaemontana catharinensis: Antitumour activity, toxicity in silico and molecular modelling studies. , 2019, Bioorganic chemistry.

[10]  A. Ruiz,et al.  Synthesis, characterization, crystal structure and in vitro antiproliferative assays of the 2-thiouracilato(triphenylphosphine)gold(I) complex , 2019, Journal of Molecular Structure.

[11]  A. Simões,et al.  Brazilian Tabernaemontana genus: Indole alkaloids and phytochemical activities. , 2016, Fitoterapia.

[12]  P. F. Oliveira,et al.  Cytotoxicity screening of essential oils in cancer cell lines , 2015 .

[13]  Carolina Nazareth Matozinhos,et al.  Diversidade taxonômica de Apocynaceae na Serra Negra, MG, Brasil , 2011 .

[14]  G. Cragg,et al.  In vitro anticancer screening of South African plants. , 2008, Journal of ethnopharmacology.

[15]  A. Nemes,et al.  Synthesis of metabolites of cis and trans apovincamine derivatives , 2008 .

[16]  A. D. Oliveira,et al.  Chemical constituents from Tabernaemontana catharinensis root bark: a brief NMR review of indole alkaloids and in vitro cytotoxicity , 2008 .

[17]  J. Boustie,et al.  Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. , 2003, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[18]  M. Nicoletti,et al.  Antiplasmodial activity of the alkaloids of Peschiera fuchsiaefolia. , 2009, Planta medica.

[19]  M. Suffness,et al.  Assays related to cancer drug discovery , 1999 .

[20]  D. Scudiero,et al.  Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. , 1991, Journal of the National Cancer Institute.

[21]  T. V. van Beek,et al.  Tabernaemontana L. (Apocynaceae): a review of its taxonomy, phytochemistry, ethnobotany and pharmacology. , 1984, Journal of ethnopharmacology.