Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics.

This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor ß((ERß) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics.

Preparation of Isodehydrodigallic Acid Using Ullmann Condensation.

Isodehydrodigallic acid, which is an important component of several ellagitannin compounds, was easily synthesized using a classical Ullmann condensation reaction.

Preparation and Evaluation of Gallate Ester Derivatives Used as Promising Antioxidant and Antibacterial Inhibitors.

Many gallate esters have been applied as food additives due to their good biological properties. Herein, nine novel gallate ester derivatives were synthesized by a Friedel-Crafts alkylation reaction and characterized by melting point (m.p.), infrared (IR) spectroscopy, nuclear magnetic resonance (1 H- and 13 C-NMR) spectra, and high-resolution mass spectrometry (HR-ESI-MS). Their antioxidant and antibacterial activities were measured using a series of classical assays. Studies found that the products showed favorable antioxidant and antibacterial activities. Their 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH⋅ ) scavenging effect IC50 values were less than 5.00 µg mL-1 and their reducing power was not less than that of vitamin C (Vc). Furthermore, the antibacterial results showed that the minimum inhibitory concentration (MIC) values of the products were not greater than 8.00 µg mL-1 , and their antibacterial rates were over 95 % at 300 µg mL-1 . The above data add valuable and novel information that gallate ester derivatives can be considered potential food additives to address food safety issues because of their high biological activity and health benefits.

Synthesis, characterization, antidiabetic and antioxidative evaluation of a novel Zn(II)-gallic acid complex with multi-facet activity.

OBJECTIVES: This study was done to synthesize a novel Zn(II)-gallic acid complex with improved antidiabetic and antioxidative properties. METHODS: The complex was synthesized and characterized using Fourier Transform Infrared (FT-IR) and 1 H NMR. Cytotoxicity was evaluated using Chang liver cells and L6 myotubes. Radical scavenging and Fe3+ -reducing, as well as α-glucosidase, α-amylase and glycation inhibitory properties were measured. Glucose uptake was measured in L6 myotubes, while the complex was docked against glucose transporter type 4 (GLUT-4) and protein kinase B (PKB). KEY FINDINGS: Analysis showed that complexation occurred through a Zn(O4 ) coordination; thus, the complex acquired two moieties of gallic acid, which suggests why complexation increased the DPPH (IC50  = 48.2 µm) and ABTS (IC50  = 12.7 µm) scavenging and α-glucosidase inhibitory (IC50  = 58.5 µm) properties of gallic acid by several folds (5.5, 3.6 and 2.7 folds; IC50  = 8.79, 3.51 and 21.5 µm, respectively). Zn(II) conferred a potent dose-dependent glucose uptake activity (EC50  = 9.17 µm) on gallic acid, without reducing the viability of L6 myotubes and hepatocytes. Docking analysis showed the complex had stronger interaction with insulin signalling proteins (GLUT-4 and PKB) than its precursor. CONCLUSIONS: Data suggest that complexation of Zn(II) with gallic acid resulted in a complex with improved and multi-facet antioxidative and glycaemic control properties.

Amide derivatives of Gallic acid: Design, synthesis and evaluation of inhibitory activities against in vitro α-synuclein aggregation.

Gallic acid (GA), a natural phenolic acid, has received numerous attention because of its anti-oxidative, anti-inflammatory, and anti-cancer activity. More importantly, GA can act as an efficient inhibitor of α-Synuclein (α-Syn) aggregation at early stages. Nevertheless, some evidences suggest that GA is unlikely to cross the blood-brain barrier because of its high hydrophilicity. Hence, GA may not be considered as a promising candidate or entering brain and directly affecting the central nervous system. Accordingly, we have designed and synthesized a series of amide derivatives of GA, some of which possess appropriate lipophilicity and hydrophilicity with LogP (2.09-2.79). Meanwhile, these sheet-like conjugated compounds have good π-electron delocalization and high ability of hydrogen-bond formation. Some compounds have shown better in vitro anti-aggregation activities than GA towards α-Syn, with IC50 down to 0.98 µM. The valid modification strategy of GA is considered an efficient way to discover novel inhibitors of α-Syn aggregation.

Design and synthesis of novel SCM-198 analogs as cardioprotective agents: Structure-activity relationship studies and biological evaluations.

SCM-198 (Leonurine) has attracted great attention due to its cardioprotective effects in myocardial infarction (MI). However, no systematic modifications and structure-activity relationship (SAR) studies could be traced so far. In this study, 35 analogs of SCM-198 were designed, synthesized and their cardioprotective effects were evaluated. The cell viability assay on cardiomyocyte cell line H9c2 challenged with H2O2 showed that several analogs exhibited more potent cytoprotective effects than SCM-198 at 1 µM and 10 µM concentrations. LDH release level in cells treated with 1 µM 14o was comparable with cells treated with 10 µM SCM-198. Results of Bcl-2 expression and caspase-3 activation accordingly indicated higher protective activity of 14o than SCM-198. Moreover, in a mouse model of MI, the mice pretreated with 14o had much lower infarct size compared with that of SCM-198. The mechanism study suggested that 14o improved cardiac morphology and reduced apoptosis of cardiomyocytes in the border zone of infarction, as proved by H&E and TUNEL staining.

Computational Analysis and Synthesis of Syringic Acid Derivatives as Xanthine Oxidase Inhibitors.

BACKGROUND: Xanthine oxidase (XO; EC 1.17.3.2) has been considered as a potent drug target for the cure and management of pathological conditions prevailing due to high levels of uric acid in the bloodstream. The role of xanthine oxidase has been well established in the generation of hyperuricemia and gout due to its important role in catalytic oxidative hydroxylation of hypoxanthine to xanthine and further catalyses of xanthine to generate uric acid. In this research, syringic acid, a bioactive phenolic acid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. OBJECTIVE: The study aimed to develop new xanthine oxidase inhibitors from natural constituents along with the antioxidant potential. METHODS: In this report, we designed and synthesized syringic acid derivatives hybridized with alcohol and amines to form ester and amide linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. RESULTS: Results of the study revealed that SY3 produces very good xanthine oxidase inhibitory activity. All the compounds showed very good antioxidant activity. The enzyme kinetic studies performed on syringic acid derivatives showed a potential inhibitory effect on XO ability in a competitive manner with IC50 value ranging from 07.18µM-15.60µM and SY3 was revealed as the most active derivative. Molecular simulation revealed that new syringic acid derivatives interacted with the amino acid residues SER1080, PHE798, GLN1194, ARG912, GLN 767, ALA1078 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential. CONCLUSION: Molecular docking proved to be an effective and selective tool in the design of new syringic acid derivatives .This hybridization of two natural constituents could lead to desirable xanthine oxidase inhibitors with improved activity.

An activatable near-infrared fluorescent probe for methylglyoxal imaging in Alzheimer's disease mice.

Visual detection of the methylglyoxal (MGO) level in the brain is critical for understanding its role in the onset and progression of AD. Herein, we disclosed a NIR fluorescent probe, DBTPP, for detecting MGO by utilizing a thiadiazole-fused o-phenylenediamine moiety as a MGO-specific sensing unit. DBTPP exhibits a series of distinct advantages, such as NIR emission, high selectivity and sensitivity, excellent acid-stability, and a huge off-on ratio. The probe could accurately monitor both exogenous and endogenous MGO variations in SH-SY5Y cells. Besides, it was able to image the endogenous MGO in a transgenic AD mouse model successfully, suggesting the great potential of MGO as a biomarker for early AD diagnosis.

Synthesis and Comparative Structure-Activity Study of Carbohydrate-Based Phenolic Compounds as α-Glucosidase Inhibitors and Antioxidants.

Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro-d-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.

Optimization and anti-inflammatory evaluation of methyl gallate derivatives as a myeloid differentiation protein 2 inhibitor.

Myeloid differentiation protein 2 (MD2) is a co-receptor of toll-like receptor 4 (TLR4) responsible for the recognition of lipopolysaccharide (LPS) and mediates a series of TLR4-dependent inflammatory responses in inflammatory lung diseases including acute lung injury (ALI). Targeting MD2 thus may provide a therapeutic strategy against these lung diseases. In this study, we identified a novel compound 4k with the potent anti-inflammatory activity among 39 methyl gallate derivatives (MGDs). MGD 4k exhibited a high binding affinity to MD2, which in turn prevented the formation of the LPS/MD2/TLR4 complex. In addition, MGD 4k significantly reversed the upregulation of LPS-induced inflammatory mediators such as tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in vitro and in vivo. Mechanistically, MGD 4k performed anti-inflammatory function by inactivating JNK, ERK and p38 signaling pathways. Taken together, our study identified MGD 4k as a novel potential therapeutic agent for ALI through inhibiting MD2, inflammatory responses, and major inflammation-associated signaling pathways.

Synthesis of dual functional gallic-acid-based carbon dots for bioimaging and antitumor therapy.

Carbon quantum dots are excellent photoluminescent materials because of their unique fluorescence properties. They are widely used in biomedical imaging due to their good biocompatibility. However, carbon quantum dots with antitumor activity have rarely been reported. Gallic acid (GA) is an anticancer agent and effective against many types of tumor cells. In this study, GA based carbon dots (GACDs) with fluorescence and antitumor activity were synthesized by a simple microwave-assisted method and characterized by transmission electron microscopy (TEM), and Fourier transformed infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). Studies of optical properties indicated that the GACDs exhibited significant photoluminescence. In addition, we observed the antitumor activity of the GACDs using both cell-based assays and mouse xenograft tumors. Our results demonstrated that the GACDs can be used as both a bioimaging material and an antitumor agent, suggesting their great potential in future clinical applications.

Design and screening of syringic acid analogues as BAX activators-An in silico approach to discover "BH3 mimetics".

Although BAX, which is a molecular hit squad that incentive apoptosis was found to be an attractive emerging target for anticancer agents. The molecular mechanism of small molecules/peptides involved in the BAX activation was remain unknown. The present focus of the study is to identification and development of novel molecules which are precisely activates BAX mediated apoptosis. In this process we identified some syringic acid analogues associated with the BAX hydrophobic groove by a virtual-screen approach. Results from the docking studies revealed that, SA1, SA9, SA10, SA14 and SA21 analogues have shown good interaction with BAX trigger site, of which SA10 and SA14 bound specifically with Lys21 at α1 helix of BAX, a critical residue involved in BAX activation. All docking calculations of SA analogues were compared with clinically tested BH3 mimetics. In this entire in silico study, SA analogous have performed an ideal binding interactions with BAX compared to BH3 mimetics. Further, in silico point mutation of BAX-Lys21 to Glu21 resulted in structural change in BAX and showed reduced binding energy and hydrogen bond interactions of the selected ligands. Based on these findings, we propose that virtual screening and mutation analysis of BAX is found to be the critical advance method towards the discovery of novel anticancer therapeutics.

The Synthesized Plant Metabolite 3,4,5-Tri-O-Galloylquinic Acid Methyl Ester Inhibits Calcium Oxalate Crystal Growth in a Drosophila Model, Downregulates Renal Cell Surface Annexin A1 Expression, and Decreases Crystal Adhesion to Cells.

The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) model were investigated. Membrane, cytosolic, and total annexin A1 (AxA1), α-enolase, and heat shock protein 90 (HSP90) amounts were examined by Western blot analysis after subcellular fractionation, then confirmed by immunofluorescence staining of cultured cells. Pretreatment of MDCKI cells with TGAME for up to 6 h significantly diminished COM crystal binding in a concentration-dependent manner. TGAME significantly inhibited AxA1 surface expression by immunofluorescence microscopy, whereas intracellular AxA1 increased. Western blot analysis confirmed AxA1 expression changes in the membrane and cytosolic fractions of compound-treated cells, whereas whole cell AxA1 remained unchanged. TGAME also significantly decreased the size, number, and growth of calcium oxalate (CaOx) crystals induced in a Drosophila melanogaster MT model and possessed a potent antioxidant activity in a DPPH assay.

Discovery of Leonuri and therapeutical applications: From bench to bedside.

Despite several advances in percutaneous coronary intervention and the discovery of new drugs, the incidence of myocardial infarction and deaths due to cardiovascular diseases (CVD) has not decreased markedly in China. The quality of life is affected seriously, which further results in great social and family burden. Many drugs, from the century-old aspirin to the newly FDA-approved Byvalson, have been proven to be effective in the treatment and prevention of CVD. As clinically reported, those life-saving drugs still have their side effects in regards to the narrow therapeutic indexes influenced by individual genetic variations. Herba Leonuri, also known as Chinese Motherwort, which are naturally present in plants and traditionally are used for the uterotonic action, postpartum blood stasis, breast pain as well as other gynecological disorders in China for thousands of years. Since the last two decades, our group has reported leonurine, a unique alkaloid found in Herba Leonuri, exhibits various bioactivities such as antioxidant, anti-apoptotic effects, free radical scavenging and anti-inflammatory effects, in addition to improving micro-circulation. These bioactivities are related to the underlying mechanisms of ischemic heart diseases and cardiac fibrosis. Pharmacological studies have proven leonurine to be effective in treating CVD in various ways, particularly ischemic heart diseases. Besides the cardio protective effects, which are similar in the central nervous system, more specifically, inhibited mitochondrial reactive oxygen species production together with the restored mitochondrial function and redox state were observed in middle cerebral artery occlusion rats by leonurine treatment, which strongly reveals its neuroprotective effects and carries a therapeutic potential for recovery and prevention of stroke. Based on their mode of action, we propose that leonurine can be developed as drugs to treat ischemic heart diseases. Taking advantage of the most recent findings in pharmacological research including the effects of low toxicity and good pharmacokinetics characteristics, leonurine has a very attractive prospect of clinical application. Our recent promising pharmacological results may be able to eradicate the barrier hindering its sale on market. In sum, from bench to bedside is no longer a long way for leonurine.

Tetramer as efficient structural mode for organizing antioxidative carboxylic acids: The case in inhibiting DNA oxidation.

To overcome the problem on the relationship of antioxidative effect with the branch number in a tetramer, we herein designed a series of antioxidants with pentaerythritol, glycerol, and ethylene glycol as the cores, and gallic, ferulic, caffeic, and p-hydroxybenzoic acids as the antioxidative moieties. In the case of DNA oxidation mediated by 2,2'-azobis(2-amidinopropane hydrochloride, AAPH), it was found that the stoichiometric factor (n) of a carboxylic acid increased rapidly when the acid was esterified with ethylene glycol, glycerol, and pentaerythritol to form a dimer, trimer, and tetramer, respectively. Interestingly, the coefficient in the equation of n∼{branch} ({branch} referred to the number of branches) was higher than one, indicating that the antioxidative effect was enhanced more promptly than the increase of the number of branches. Meanwhile, tetramer exhibited high intercalation effect with DNA strand. Therefore, additionally antioxidative effect was ascribed to the tethering effect resulting from tetrameric structure and strong intercalation with DNA strand generated by tetramer.

Novel hamamelitannin analogues for the treatment of biofilm related MRSA infections-A scaffold hopping approach.

Antimicrobial research is increasingly being focused on the problem of resistance and biofilm formation. Hamamelitannin (HAM) was recently identified as an antimicrobial potentiator for conventional antibiotics towards Staphylococcus aureus. This paper describes the synthesis and biological evaluation of novel hamamelitannin analogues with alternative central scaffolds. Via a ligand-based approach, several interesting compounds with improved synthetic accessibility were identified as potentiators for vancomycin in the treatment of MRSA infections.

Synthesis, Biological Evaluation, and Docking Studies of a Novel Sulfonamido-Based Gallate as Pro-Chondrogenic Agent for the Treatment of Cartilage.

Gallic acid (GA) and its derivatives are anti-inflammatory agents and are reported to have potent effects on Osteoarthritis (OA) treatment. Nonetheless, it is generally accepted that the therapeutic effect and biocompatibility of GA is much weaker than its esters due to the high hydrophilicity. The therapeutic effect of GA on OA could be improved if certain structural modifications were made to increase its hydrophobicity. In this study, a novel sulfonamido-based gallate was synthesized by bonding sulfonamide with GA, and its biological evaluations on OA were investigated. Results show that 5-[4-(Pyrimidin-2-ylsulfamoylphenyl)]-carbamoyl-benzene-1,2,3-triyl triacetate (HAMDC) was able to reverse the effects induced by Interleukin-1 (IL-1) stimulation, and it also had a great effect on chondro-protection via promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as well as enhancing synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Furthermore, a docking study showed that HAMDC fits into the core of the active site of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), which provides an explanation for its activity and selectivity.

The Synthesis of trans-Flavan-3-ol Gallates by Regioselective Oxidative Etherification and Their Cytotoxicity Mediated by 67 LR.

We report on a chiral pool approach for the synthesis of trans-flavan-3-ol gallates from epichlorohydrin. The trans-flavan-3-ol gallates were prepared by the cycloetherification of the phenol at the C2 benzylic position of 2-acylozyl-1,3-diarylpropane during regioselective C-H oxidation. The 1,3-diarylpropanes were prepared starting from epichlorohydrin by epoxide opening with A and B ring precursors, followed by acylation of the resultant alcohol with galloyl chloride. The availability of both the enantiomers of epichlorohydrin allowed the preparation of the corresponding enantiomer using the same procedure. The cytotoxicity of the compounds against U266 cells was tested, in which 5-deoxy-7,3'-O-dimethyl gallocatechin gallate exhibited cytotoxicity that was more than ten times stronger than natural (-)-EGCG. In addition, the absolute configuration of the derivatives did not critically affect the biological activity.

Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production.

Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control.

Identificación de ácidos polifenólicos en el extracto metanólico de las hojas de terminalia catappa Linn / Identification of polyphenolic acids in the methanolic extract from Terminalia catappa Linn leaves

INTRODUCCIÓN: diferentes extractos de Terminalia Catappa Linn. (Combretaceae) han demostrado de forma internacional, propiedades farmacológicas beneficiosas para la salud humana. Estas propiedades han sido atribuidas en lo fundamental a los polifenoles y glicósidos, encontrados en hojas, corteza y frutos. En Cuba esta especie es catalogada como una planta invasora y existen pocas investigaciones sobre su composición química y estudios farmacológicos. OBJETIVOS: identificar y cuantificar los ácidos polifenólicos presentes en el extracto metanólico de las hojas de T. catappa utilizándose la cromatografía de gases acoplada a espectrometría de masas. MÉTODOS: las hojas amarillo-rojizas fueron secadas, molidas, desgrasadas con hexano y y con posterioridad extraídas con metanol en un baño ultrasónico. El extracto se filtró y el disolvente se eliminó al vacío. El extracto seco se hidrolizó con ácido clorhídrico y se extrajo con acetato de etilo. Se determinó el rendimiento de extracción, las características organolépticas y los polifenoles totales mediante el método de Follin-Ciocalteu. La composición química del extracto hidrolizado se llevó a cabo por cromatografía de gases acoplada a espectrometría de masas, previa formación de los derivados trimetilsilil. RESULTADOS: se obtuvo un líquido de color pardo rojizo oscuro de olor característico. El contenido total de polifenoles fue 184,6 (mg Pirogalol/100 g Extracto). Se detectaron 37 compuestos por cromatografía de gases acoplada a espectrometría de masas en el extracto metanólico hidrolizado. Este extracto está compuesto de manera general por ácidos polifenólicos como el ácido gálico; ácido vanílico; ácido 3,4-dihidroxibenzoico; ácido 2,5-dihidroxi-benzoico y ácido 4- hidroxibenzoico. También se detectaron otros compuestos con elevados contenidos como ácido elágico y ácido levulínico. CONCLUSIONES: el extracto metanólico de hojas de T. catappa que crece en Cuba mostró un elevado contenido de ácidos polifenólicos, donde los ácidos gálico y elágico fueron los mayoritarios. La presencia de estos compuestos pudiera justificar las propiedades medicinales atribuidas a esta especie, a la vez que servirían de base para continuar con futuras pruebas farmacológicas que avalen sus usos con fines farmacéuticos.

INTRODUCTION: Different extracts of Terminalia Catappa Linn. (Combretaceae) internationally have shown pharmacological properties beneficial to human health. These properties have been largely attributed to polyphenols and their glycosides found in the leaves, bark and fruits. In Cuba this species is listed as an invasive plant and there is limited research on its chemical composition and pharmacological studies. OBJECTIVES: To identify and quantify the polyphenolic acids that could be present in the methanol extract of Terminalia catappa leaves using gas chromatography-mass spectrometry. METHODS: The yellow-red leaves were dried, ground, defatted with hexane and then extracted with methanol in an ultrasonic bath. The extract was filtered and the solvent removed under vacuum. The dry extract was hydrolyzed with hydrochloric acid and extracted with ethyl acetate. The extraction yield, the organoleptic characteristics and the total polyphenols by Follin-Ciocalteu method were determined. The chemical composition of the hydrolyzed extract was performed by gas chromatography-mass spectrometry after formation of trimethylsilyl derivatives. RESULTS: A dark reddish brown liquid with a characteristic odor was obtained. The total polyphenol content was 184.6 (mg Pyrogallol/100g extract). By mean of gas chromatography-mass spectrometry a total of 37 compounds were detected in the hydrolyzed methanol extract. This extract consists mainly of polyphenolic acids such as gallic acid; vanillic acid; 3,4-dihydroxybenzoic acid; 2,5-dihydroxybenzoic acid and 4- hydroxybenzoic acid. Other compounds with high content as ellagic acid and levulinic acid were also detected. CONCLUSIONS: The methanolic extract obtained from the leaves of Terminalia catappa growing in Cuba showed a high content of polyphenolic acids where gallic acid and ellagic predominated. The presence of these compounds could justify the medicinal properties attributed to this species, while providing the basis for further future pharmacological evidence to support its use for pharmaceutical purposes.