Reproductive disorders may originate from many factors including exposure to environmental chemicals in the womb or during the early stages of postnatal life. Throughout these stages, the exposure to endocrine-disrupting chemicals (EDCs), such as bisphenols, can disrupt reproductive function. These compounds cross the placenta and cause long-term epigenetic alterations in the fetus. Bisphenols are a large class of chemicals mainly used in the plastic industry and epoxy resin production. Bisphenol A (BPA) was the first and most widely used compound; however, it acts as a hormone by binding to estrogen receptors (ERs), affecting estrogen-dependent functions. As a result, BPA has been replaced by analogues or similar compounds, such as bisphenol F (BPF), bisphenol S (BPS), bisphenol B (BPB), and bisphenol AF (BPAF), among others. Although these compounds were originally synthesized to be safe for human use, they have also exhibited endocrine-disrupting activity similar to BPA, which affects reproductive function. BPA analogues also induce epigenetic changes, such as DNA methylation, histone modification, chromatin remodeling, and non-coding RNA regulation. These changes can lead to reproductive disorders and negative long-term and transgenerational consequences. This narrative review includes in vivo, in vitro, and human cohort studies that examine how BPA and its analogues affect male and female reproductive function through epigenetic mechanisms. Through this pathway, these chemical compounds have the potential to modify developmental programming.

Introduction and Objectives: Insulin-like Growth Factor Binding Protein (IGFBP)-2 is lower in serum during obesity and metabolic dysfunction. We have previously shown that the decrease in serum IGFBP-2 follows a diminished expression in liver and heart, both associated with the progression of steatotic liver disease. We aimed to identify, in a murine model, the synthesis of IGFBP-2 in extrahepatic tissues involved in metabolic dysfunction: skeletal muscle and adipose tissue. Materials and Patients: Samples of hamstring muscle, and epididymal adipose tissue were obtained from male C57BL/6 mice, fed a high-fat diet supplemented with sucrose and fructose (42g/L) in the beverage during 6 months. All procedures were approved by the Institutional Committee of Care and Use of Laboratory Animals at the School of Medicine, UNAM (FM/DI/005/2022). Four groups were included: Control; Metabolic dysfunction (MD), exhibiting increased bodyweight and adiposity; MD with steatosis (MD+SS); and MD+SS with fibrosis (MD+SS+F). Total protein was isolated in a protease inhibitor cocktail. Protein integrity was assessed by SDS-PAGE. IGFBP-2 was assayed by ELISA. Data was shown as Mean±SD, analyzed by one-way ANOVA; Student´s t test was applied to compare 2 groups. P<0.05 was considered significant. Results: IGFBP-2 expression was 6-fold increased in control skeletal muscle compared to control adipose tissue. In epididymal adipose tissue, IGFBP-2 expression significantly decreased in MD+SS+F compared to Controls, and MD. In contrast, the hamstring showed increased IGFBP-2 expression in mice showing metabolic dysfunction associated with steatotic liver disease: MD+SS and MD+SS+F. The percentage of adiposity significantly increased in MD subjects whereas no changes were observed regarding muscle mass, suggesting hypertrophy might be key. Conclusions: Our results show that metabolic dysfunction (MD) associated with MASLD have a role in inhibiting IGFBP-2 expression in adipose tissue. In contrast, skeletal muscle increases its synthesis. These results suggest a role for skeletal muscle in the reversion of MASLD through IGFBP-2 expression. More studies are needed to identify the roles of skeletal muscle and its hypertrophic state in MASLD.

The prevalence of chronic metabolic diseases in Mexico is high, being type 2 Diabetes mellitus (T2DM) as the most common disease. Several studies have shown that, compared with healthy individuals, patients with T2DM suffer a higher severity and mortality of Coronavirus disease 2019 (COVID-19). Therefore, it is important to the knowledge of the bidirectional relationship between these diseases. T2DM can increase SARS-CoV-2 virus pathogenicity in part due to metabolic disturbance. As a result, COVID-19 susceptibility and severity rise in diabetic individuals, which makes them a high-risk population. On the other hand, the infection caused by SARS-CoV-2 can lead individuals to hyperglycemia or new-onset diabetes. In order to understand the relationship between COVID-19 and T2DM, this review aims to emphasize the tropism of the SARS-CoV-2 virus to pancreatic beta-cells, as well as the physiologic effects of these.

Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. Methods: The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by 1H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D2O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. Results: The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. Conclusions: The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment.

Glucotoxicity may exert its deleterious effects on pancreatic β-cell function via a myriad of mechanisms, leading to impaired insulin secretion and, eventually, type 2 diabetes. β-cell communication requires gap junction channels to be present among these cells. Gap junctions are constituted by transmembrane proteins of the connexins (Cxs) family. Two Cx genes have been identified in β cells, Cx36 and Cx30.2. We have found evidence that the glucose concentration on its own is sufficient to regulate Cx30.2 gene expression in mouse islets. In this work, we examine the involvement of the Cx30.2 protein in the survival of β cells (RIN-m5F). Methods: RIN-m5F cells were cultured in 5 mM D-glucose (normal) or 30 mM D-glucose (high glucose) for 24 h. Cx30.2 siRNAs was used to downregulate Cx30.2 expression. Apoptosis was measured by means of TUNEL, an annexin V staining method, and the cleaved form of the caspase-3 protein was determined using Western blot. Results: High glucose did not induce apoptosis in RIN-m5F β cells after 24 h; interestingly, high glucose increased the Cx30.2 total protein levels. Moreover, this work found that the downregulation of Cx30.2 expression in high glucose promoted apoptosis in RIN-m5F cells. Conclusion: The data suggest that the upregulation of Cx30.2 protects β cells from hyperglycemia-induced apoptosis. Furthermore, Cx30.2 may be a promising avenue of therapeutic investigation for the treatment of glucose metabolic disorders.

Introduction and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide, the concomitant presence of fibrosis is considered the most important risk factor of cardiovascular death. IGFBP2 is expressed mainly in the liver and at very low levels in heart. This peptide is associated with metabolic affection including obesity and type 2 diabetes. IGFBP2 role in MASLD is not clear. We aimed to assess the expression of IGFBP2 protein in the liver and associate it with its blood levels and cardiac expression in a rodent model of MASLD. Materials and Patients: Male C57BL/6 mice weighing 23±2g were included and fed a high-fat diet with water added with sugar (HF-SF) or control diet up to 30 weeks. Liver damage was assessed by biopsy. IGFBP2 was assayed by ELISA in serum, liver, and heart. Data is shown as Mean±SD, analyzed by ANOVA, p<0.05. Results: HF-SF mice exhibited increased bodyweight, visceral adiposity, and fasting glycemia compared to controls. HF-SF group developed steatosis with or without fibrosis. Mice showing fibrosis were assessed as F1C, portal fibrosis. IGFBP2 was significantly lower in steatosis regardless of the presence of fibrosis, both in serum and liver. Cardiac expression of IGFBP2 was diminished in steatosis with fibrosis compared with controls. Significant, moderate, positive correlations were observed between serum IGFBP2 and its hepatic expression, as well as IGFBP2 cardiac expression. IGFBP2 in serum negatively correlated with visceral adiposity and bodyweight. Conclusions: IGFBP2 expression in liver and heart depends on the stage of MASLD and is associated with visceral adiposity. IGFBP2 in the bloodstream is produced mainly by the liver, and with lower contribution from heart. Serum IGFBP2 can be considered as a marker of its hepatic and cardiac expressions which are closely related with the stage of MASLD. IGFBP2 might be considered a molecular link between liver and heart during MASLD.

Carbendazim derivatives, commonly used as antiparasitic drugs, have shown potential as anticancer agents due to their ability to induce cell cycle arrest and apoptosis in human cancer cells by inhibiting tubulin polymerization. Crystallographic structures of α/β-tubulin multimers complexed with nocodazole and mebendazole, two carbendazim derivatives with potent anticancer activity, highlighted the possibility of designing compounds that occupy both benzimidazole- and colchicine-binding sites. In addition, previous studies have demonstrated that the incorporation of a phenoxy group at position 5/6 of carbendazim increases the antiproliferative activity in cancer cell lines. Despite the significant progress made in identifying new tubulin-targeting anticancer compounds, further modifications are needed to enhance their potency and safety. In this study, we explored the impact of modifying the phenoxy substitution pattern on antiproliferative activity. Alchemical free energy calculations were used to predict the binding free energy difference upon ligand modification and define the most viable path for structure optimization. Based on these calculations, seven compounds were synthesized and evaluated against lung and colon cancer cell lines. Our results showed that compound 5a, which incorporates an α-naphthyloxy substitution, exhibits the highest antiproliferative activity against both cancer lines (SK-LU-1 and SW620, IC50 < 100 nM) and induces morphological changes in the cells associated with mitotic arrest and mitotic catastrophe. Nevertheless, the tubulin polymerization assay showed that 5a has a lower inhibitory potency than nocodazole. Molecular dynamics simulations suggested that this low antitubulin activity could be associated with the loss of the key H-bond interaction with V236. This study provides insights into the design of novel carbendazim derivatives with anticancer activity.

5α,8α-peroxyergosteryl divaricatinate (1) is isolated for the first time from acetone extract of the thallus of Cladonia cf. didyma together with condidymic (2), isodidymic (3) and barbatic (4) acids. Their UVB/UVA photoprotective and antioxidant activities were determined along with their cyto- and DNA-protecting actions against OH• damage. Compound 1 showed high UVA, cyto- (%cell viability ca. 82 at 15 µM vs 71 for OH•) and DNA (%DNA-integrity ca. 74 at 100 µM vs 22 for OH•) protecting properties. Compounds 2 and 3 exhibited high UVB (SPF ca. 40) and antioxidant activities (free radical scavenging potency EC50 = 0.6694 and 1.700 mol compound/mol DPPH•; ferric reducing power 0.392 and 0.546, at 500 ppm and inhibited lipid peroxidation); protecting cells (%cell viability ca. 76 at 15 µM) and DNA (%DNA-integrity ca. 57 at 100 µM). Compounds 1 to 3 fulfilled some physicochemical properties to act topically on the skin.

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four β-cyclodextrin (βCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the βCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-βCD platforms and the classical PAMAM-βCD dendrimer. Finally, we determined the toxicity for all EDTA-βCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-βCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

Autophagy is a crucial mechanism for the functioning and survival of pancreatic beta cells. Its dysregulation has been associated with obesity, insulin resistance, and glucose intolerance. Furthermore, decreased autophagy in insulin-secret ing beta cells has been reported to contribute to the devel opment of type 2 diabetes mellitus (T2DM), which constitutes about 95% of all diabetes cases and is a chronic metabolic disease that it currently affects millions of people around the world. In different models of rodents, whether diabetic or obese, it has been observed that treatment with autophagy enhancers lowers glucose levels, increases insulin sensitivity, and protects beta cells from apoptosis. As stated above, it has recently been proposed to carry out an early intervention in patients with T2DM, using drugs that promote autophagy, which could help preserve the mass of beta cells and prevent the progression of the disease. This review provides an over view of the importance of the physiological process of auto phagy and its imminent role in the development of T2DM. Keywords: Pancreatic beta cells; autophagy; cell death; diabetes mellitus type 2

Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC50 of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5.

In the last years, diminished ovarian reserve (DOR) is becoming a frequent pathology in the human reproductive system, which also has a major impact on quality of life and fertility of reproductive age women. However, DOR remains as a disease of unknown etiology. The aim of this study was to assess the differential expression levels of multipotent stem cell markers in the ovarian surface epithelium (OSE) of women with DOR and women with adequate ovarian reserve (AOR) that could be associated with the loss of ovarian functionality. Methods: The present study was performed by using ovary tissue samples from patients previously diagnosed as AOR and DOR according to the clomiphene citrate challenge test. The expression levels of multipotent stem cell and germline markers were analyzed by immunohistochemistry. Results: Our findings demonstrate that a small number of epithelial cells express the Oct4 stem cell marker and the specific germ line markers (Fragilis, Stella, and VASA) in the OSE of both AOR and DOR patients, but the number of immunostained cells were lower in the women with AOR than DOR individuals. On the other hand, the expression of SOX2 and Nanog stem cell markers was only observed in the OSE of DOR women but not in AOR patients. Conclusions: The overall results of this study show that there is a differential expression of stem cell markers in the OSE cells from DOR women as compared with AOR subjects, suggesting a possible compensatory mechanism for the generation of new multipotent cells to participate in the repair and/or renewal of the population of ovary cells in the OSE of DOR women.

Ethnopharmacological relevance: The use of medicinal plants in Mexico has been documented since pre-Hispanic times. Nevertheless, the level of use of medicinal plants by health professionals in Mexico remains to be explored.Aim of the study: To evaluate the use, acceptance and prescription of medicinal plants by health professionals in 9 of the states of Mexico.Materials and methods: Direct and indirect interviews, regarding the use and acceptance of medicinal plants, with health professionals (n=1614), including nurses, physicians, pharmacists, and odontologists from nine states in Mexico were performed from January 2015 to July 2016. The interviews were analyzed with the factor the informant consensus (FIC).Results: The information obtained indicated that 46% of those interviewed feel patients should not use medicinal plants as an alternative therapy. Moreover, 54% of health professionals, and 49% of the physicians have used medicinal plants as an alternative therapy for several diseases. Twenty eight percent of health professionals, and 26% of the physicians, have recommended or prescribed medicinal plants to their patients, whereas 73% of health professionals were in agreement with receiving academic information regarding the use and prescription of medicinal plants. A total of 77 plant species used for medicinal purposes, belonging to 40 botanical families were reported by the interviewed. The results of the FIC showed that the categories of diseases of the digestive system (FIC=0.901) and diseases of the respiratory system (FIC=0.898) had the greatest agreement.Conclusions: This study shows that medicinal plants are used for primary health care in Mexico by health professionals.

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

OBJECTIVE:To design and synthesize an orcinol derivative compound, 3-formyl-2,4-dihydroxy-5,6-dimethyl sodium benzoate (A4), as an antioxidant molecule and to test its effects on oxidative stress in an in-vitro model of apoptosis of pancreatic rat beta cells induced by streptozotocin (STZ).METHODS:Scavenger properties of A4 were assessed using its capacity to capture the DPPH radical in vitro. Antiapoptotic properties of A4 were analysed by electron microscopy and TUNEL assay in rat pancreatic islets in a streptozotocin model.KEY FINDINGS:The results show that A4 displays antioxidant activity in in-vitro assays and induced a significant reduction in STZ-induced beta cell apoptosis and low ultrastructural damage to cellular organelles in the rat pancreatic islets as evidenced by electronic microscopy, this effect could be attributed to its antioxidant activity in a similar manner than resveratrol.CONCLUSION:The overall results indicate that the new orcinol derivative molecule displays both antioxidant and antiapoptotic effects and protect pancreatic beta cells against STZ damage.

ABSTRACT Purpose: This study was designed to investigate whether estradiol is related to the expression of the chemokine receptor CXCR4 and its activation in lung adenocarcinoma in vitro, since lung adenocarcinomas from premenopausal women have shown high levels of CXCR4, and this expression has been associated with worse prognosis and poor survival. Methods: The effect of 17-β-estradiol (E2) (0.03 nM-10 nM) on CXCR4 expression was analyzed in lung adenocarcinoma cell lines (SK-LU-1, H1435, H23, A549) by immunofluorescence after 24 and 72-h poststimulation. Tamoxifen treatment was applied to corroborate the estrogenic effect. The wound-healing assay was performed to investigate whether E2 treatment increased CXCR4/CXL12 pathway activity. A549 and SK-LU-1 cells were stimulated with E2, CXCL12, and CXCL12 combined with E2. Tamoxifen and AMD3100 were applied to corroborate estrogen and chemokine pathway activation. Results: Estradiol stimulated significantly CXCR4 overexpression in all the cell lines analyzed in a dose- and a time-dependent manner. Tamoxifen treatment inhibited the CXCR4 overexpression observed in estrogen-treated groups, demonstrating that estrogen strongly influences CXCR4 expression in lung adenocarcinoma cells. Cells treated with E2, CXCL12 and E2 combined with CXCL12 exhibited significant cell migration, which was suppressed when tamoxifen and AMD3100 were present. Conclusion: Overexpression of CXCR4 induced by estrogen and the activity of CXCL12/CXCR4 pathway could be a new mechanism by which this hormone supports tumor progression and metastasis. These findings may partly explain the worse prognosis observed in premenopausal women and suggest considering the role of estrogen in lung cancer for the design of more specific treatment schemes.

9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinolone (D3ClP) is a bioisostere of N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide (m-AMSA) a DNA topoisomerase II inhibitor with proven cytotoxic activity and known to induce DNA damage and apoptotic cell death in K562 cells. However, recent evidence is not consistent with DNA topoisomerase II (DNA TOP2) as the primary target of D3ClP, in contrast to m-AMSA. We provide evidence of histone γH2AX phosphorylation at Ser135 in HeLa cells treated with D3ClP, a marker of DNA double strand repair through Mre11-Rad50-Nbs1 (MRN) pathway. Using two-dimensional gel electrophoresis and mass spectrometry, the upregulation of the protein GRP78, the cleavage of Cytokeratin 18, and the downregulation of prothymosine, calumenin, and the α chain of the nascent polypeptide associated complex were observed in HeLa cells treated with D3ClP. An increase in GRP78 has been related with the onset and progression of the unfolded protein response (UPR), a process aimed to reduce endoplasmic reticulum (ER) stress and protein misfolding. The IRE1-α dependent splicing of mRNA encoding X-box binding protein 1 was detected. Microtubule-associated Proteins 1A/1B, Light Chain 3-II (LC3b-II) accumulation was observed, and suggest some involvement of autophagy. The production of the pro-apoptotic protein DNA-damage-inducible protein 153 (GADD-153) was also detected. These results, are consistent with the induction of the UPR and the DNA-Damage Response in D3ClP-treated HeLa cells, and are also consistent with a concurrent apoptotic cell death. J. Cell. Biochem. 118: 1164-1173, 2017. © 2016 Wiley Periodicals, Inc.

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. (C) 2016 Elsevier Ltd. All rights reserved.

Tropical trees of Calophyllum genus (Calophyllaceae) have chemical and biological importance as potential source of secondary active metabolites which can lead to the development of new drugs. Research on this species has been rising since 1992 due to the discovering of anti-HIV properties of Calanolide A found in Calophyllum inophyllum leaves. This compound is the most important natural product for potential development of new anti-HIV drugs and phytomedicines. The scientometric analysis (1953---2014) here performed revealed that the most studied species of Calophyllum genus are: C. inophyllum and C. brasiliense, distributed in the Asian, and American continents, respectively. Current research on these species is carried out mainly in India and Brazil, respectively, where these species grow. Research on C. brasiliense is focused mainly on ecological, antiparasitic, cytotoxic properties, and isolation of new compounds. Chemical studies and biodiesel development are the main topics in the case of C. inophyllum. Text mining analysis revealed that coumarins, and xanthones are the main secondary active metabolites responsible for most of the reported pharmacological properties, and are potential compounds for the treatment of leukemia and against intracellular parasites causing American Trypanosomiasis and Leshmaniasis. On the other hand, C. inophyllum represents an important source for the development of 2nd generation biodiesel. Medicinal and industrial applications of these species may impulse sustainable forest plantations. To our knowledge this is the first scientometric and text mining analysis of chemical and biomedical research on Calophyllum genus, C. brasiliense and C. inophyllum.