Zoopharmacognosy is the multidisciplinary approach of the self-medication behavior of many kinds of animals. Recent studies showed the presence of antitumoral secondary metabolites in some of the plants employed by animals and their use for the same therapeutic purposes in humans. Other related and sometimes confused term is Zootherapy, which consists on the employment of animal parts and/or their by-products such as toxins, venoms, etc., to treat different human ailments. Therefore, the aim of this work is to provide a brief insight for the use of Zoopharmacology (comprising Zoopharmacognosy and Zootherapy) as new paths to discover drugs studying animal behavior and/or using compounds derived from animals. This work is focused on the approaches related to cancer, in order to propose a new promising line of research to overcome multidrug resistance (MDR). This novel subject will encourage the use of new alternative prospective ways to find new medicines.

The huge impact of cancer is a big concern nowadays. Protein Kinases (PKCs) are attractive anticancer targets due to their involvement in several processes of carcinogenesis. Particularly, the isoform δ (PKC-δ) acts as tumor suppressor in colon cancer, one of the most dominant cancers and cause of cancer mortality worldwide [1]. Promising bioactive molecules were found in Plectranthus genus, mainly diterpene royleanones [1, 2]. The 7α-acetoxy-6β-hydroxyroyleanone (Roy) is the major constituent of P. grandidentatus acetonic extracts. Several biological activities of Roy were reported in the literature, including antitumoral activity [3]. Moreover, the presence of two free hydroxyl groups (position C-6 and C12) in Roy structure drawn our attention to the possibility of preparing new derivatives with enhanced cytotoxic activity. In fact, in a previous work, the patented diterpene 6β-benzoyloxy-12-O-benzoylroyleanone (RoyBz) [3], shown selective activation of PKC-δ [5]. The aim of the present work is to prepare new potential PKC-δ activators from derivatization of Roy. Thus, Roy and RoyBz assisted the design of theoretical derivatives, through modification of C-12 and C-6 hydroxyl groups. Molecular docking simulations were carried out against the 3D structure of human PKC-δ regulatory domain, to identify the potential PKC-δ activators. The most promising compounds accepted by docking simulations are currently been prepared by hemi-synthesis using Roy as starting material for structure-activity relationships. References: [1]. Ladeiras D et al. (2016) Curr. Pharm. Des. 22 (12): 1682.[2]. Matias D et al. (2019) ACS Omega. 4: 8094.[3]. Bernardes CES et al. (2018) Mol. Pharm. 15 (4): 1412.[4]. Saraiva L et al., “Roy-Bz: a small molecule activator of Protein Kinase Cdelta (PKCDelta)” Patent Ref PCT/IB2017/050633.[5]. Bessa C et al., Cell Death Dis. 2018, Vol. 9.

Tuberculosis (TB) infects thousands of people every year and is a serious public health problem worldwide. The causative agent, Mycobacterium tuberculosis, is a bacterium that has elaborated survival mechanisms in the host. The discovery of new antibiotics is essential for reducing TB deaths and natural products offer an excellent starting point for the discovery of these compounds due to their structural and functional diversity. The genus Plectranthus belonging to the Lamiaceae family, such as mint and sage, exhibit a wide range of ethnobotanical uses. The P.ornatus species has diuretic, antipyretic, analgesic, antibiotic and anti-inflammatory properties and is used to relieve stomach and liver disorders. Halimane's backbone diterpene (11R*-acetoxy-halima-5,13E-dien-15-oic acid) was previously isolated for the first time from an acetone extract of P.ornatus. This compound is described due to its antimicrobial, namely antitubercular activity. Thus, in this work, for a large-scale of the compound isolation, we optimized its extraction. Moreover, an acetonic ultrasound extraction was performed (extraction yield 7.082% (w / w)). Chromatographic isolation of 5.3 mg of pure diterpene, identified by HPLC-DAD, was also performed by comparison with an authentic sample. In future studies, it will be possible the exhaustive isolation of the diterpene of this extract allowing new biological studies with potential for the development of new tuberculostatic drugs.