Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Review Indole alkaloids: 2012 until now, highlighting the new chemical structures and biological activities Pauline Fagundes Rosales a,b , Gabriela Sandri Bordin a , Adriana Escalona Gower a , Sidnei Moura a, ⁎ a LBIOP – Laboratory of Biotechnology of Natural and Synthetics Products, Technology Department, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil b IFRS -Federal Institute of Education, Science and Technology of Rio Grande do Sul, Campus Bento Gonçalves, Brazil ARTICLEINFO Keywords: Indole alkaloids Secondary metabolites Biological activities ABSTRACT Indole alkaloids have attracted attention because of their therapeutic properties, being anti-infammatory, an- tinociceptive, antitumoural, antioxidant and antimicrobial. These compounds present a wide structural diversity, which is directly related to the genera of the producing plants, as well as the biological activities. Indole al- kaloids have attracted attention over the last decade because of this combination of bioactivity and structural diversity. Therefore, this review presented recent (2012–2018) advances in alkaloids, focusing on new com- pounds, extraction methods and biological activities. As such, approximately 70 articles were identifed, which showed 261 new compounds produced by plants of the families Apocynaceae, Rubiaceae, Annonaceae and Loganiaceae. In addition, diferent extraction methods were identifed, and the structures of the new compounds were analysed. In addition to indole molecules, there were mono-indole-, di-indole-, vinblastine-, vimblastine-, gelsedine-, geissospermidine-, koumine-, geissospermidine-, iboga-, perakine-, corynanthe-, vincamine-, ajma- line-, aspidorpema-, strychnos-type, β-carboline alkaloids and indole alkaloid glucosides. The reported biological activities are mainly anticancer, antibacterial, antimalarial, antifungal, antiparasitic, and antiviral, as well as anti-acetylcholinesterase and anti-butyrylcolinesterase properties. This review serves as a guide for those wishing to fnd the most recently identifed alkaloid structures and their associated activities. 1. Introduction Secondary metabolites of plants and microorganisms, which are characterised by molecules synthesised through specifc biosynthetic routes, have been useful compounds in healthcare, and for cosmetic and food products [1]. They are the result of interactions between bio- synthesis, transport, storage and degradation processes that, through gene regulation, are guided by the main elements of heredity, devel- opment stage and the environment [2]. Secondary plant metabolites can be summarised in three groups, phenolics, terpenoids and nitrogen compounds, a broad category which includes alkaloids [3]. The alkaloids are heterocyclic compounds, generally derived from amino acids, containing one or more nitrogen atoms in its structure, which are part of the largest group of plant secondary metabolites. Among the known natural compounds, 15–20% are alkaloids, with an estimated 12,000 molecules [4]. The class is characterised by variations in nitrogen saturation (primary to quaternary), which in free base form are poorly soluble in water; however, they are soluble in organic sol- vents [5]. These compounds are more abundant in angiosperms, being represented in 25% of members [3]. The classifcation is related to the amino acid precursor [6], though biosynthetic pathway are still poorly understood [7]. In general, they can be divided into several groups based on associated moieties, for example, piperidine, pyrrolidine, pyrrole, pyriridine, quinolone, isoquinoline, indole, quinolizidine, pyrrolizidine, tropane, benzylisoquinoline, purine, β-carboline, in- dolinics and quinolizidinic [6]. The indole alkaloids, which have tryptophan or tryptamine as their precursors, are represented by more than 4000 known compounds. They have a bicyclic structure consisting of a benzene ring fused to a fve-membered pyrrole ring, and are classifed according to their bio- genic pathway in three main groups, corynanthe, aspidosperma and iboga. The diference between these molecules is the presence of https://doi.org/10.1016/j.ftote.2020.104558 Received 15 January 2020; Received in revised form 13 March 2020; Accepted 15 March 2020 Abbreviations: ADV, adenovirus; HSV, herpes simplex virus; MIA's, Monoterpenoid indole alkaloid; PE, petroleum ether; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide ⁎ Corresponding author at: Technology Department, Biotechnology Institute, University of Caxias do Sul, 1130 Francisco Getúlio Vargas st., CEP 95070-560 Caxias do Sul, Brazil. E-mail address: sidnei.moura@ucs.br (S. Moura). Fitoterapia 143 (2020) 104558 Available online 17 March 2020 0367-326X/ © 2020 Elsevier B.V. All rights reserved. T