Juan Carlos Romero Benavides - Academia.edu (original) (raw)

Papers by Juan Carlos Romero Benavides

El presente trabajo de fin de titulación: "Obtención de extractos, aislamiento y caracterización ... more El presente trabajo de fin de titulación: "Obtención de extractos, aislamiento y caracterización de metabolitos secundarios de Passiflora cumbalensis, P. manicata y P. indecora con actividad citotóxica", realizado por Karina Noemí Torres García, ha sido orientado y revisado durante su ejecución, por cuanto se aprueba la presentación del mismo.

Plants

Xylosma G. Forst. is a genus of plants belonging to the Salicaceae family with intertropical dist... more Xylosma G. Forst. is a genus of plants belonging to the Salicaceae family with intertropical distribution in America, Asia, and Oceania. Of the 100 accepted species, 22 are under some level of conservation risk. In this review, around 13 species of the genus used as medicinal plants were found, mainly in Central and South America, with a variety of uses, among which antimicrobial is the most common. There is published research in chemistry and pharmacological activity on around 15 of the genus species, centering in their antibacterial and fungicidal activity. Additionally, a variety of active phytochemicals have been isolated, the most representative of which are atraric acid, xylosmine and its derivatives, and velutinic acid. There is still ample field for the validation and evaluation of the activity of Xylosma extracts, particularly in species not yet studied, and concerning uses other than antimicrobial and for the identification and evaluation of their active compounds.

Reference Series in Phytochemistry, 2019

Additional file 1: Fig. S1. Original western blots CL-X Posure™ films for Western blots. Each pro... more Additional file 1: Fig. S1. Original western blots CL-X Posure™ films for Western blots. Each protein was detected in independent films at different times of exposure to the membrane. A) p53; B) p21; C) LC3-I and -II; D) p62; E) BAX; F) Bcl-2; G) Cleaved caspase-3; H) Active and cleaved PARP-1; I) Actin. Notice, for autophagy detection starvation control was first, in contrast to apoptosis control, which UV control was first. Fig. S2. 1H NMR spectrum of compound 3a. Fig. S3. 1H NMR spectrum of compound 3b. Fig. S4. 1H NMR spectrum of compound 3c. Fig. S5. 1H NMR spectrum of compound 3d. Fig. S6. 1H NMR spectrum of compound 3e. Fig. S7. 19F NMR spectrum of compound 2e. Fig. S8. 1H NMR spectrum of compound 3f. Fig. S9. 1H NMR spectrum of compound 3 g. Fig. S10. 13C NMR spectrum of compound 3 g. Fig. S11. FTIR spectrum of compound 3 g. Fig. S12. ESI–MS spectrum of compound 3 g. Fig. S13. 1H NMR spectrum of compound 3 h. Fig. S14. 1H NMR spectrum of compound 3i. Fig. S15. 13C NMR spectr...

Supporting Information. Synthesis and evaluation of biological activities of bis(spiropyrazolone)... more Supporting Information. Synthesis and evaluation of biological activities of bis(spiropyrazolone)cyclopropanes: a potential application against leishmaniasis

Medicinal Chemistry Research, 2017

The unique etiology of cancer requires a multidimensional approach for its treatment, control, an... more The unique etiology of cancer requires a multidimensional approach for its treatment, control, and prevention. Therefore, all approaches to drug discovery and development should be exploited. Argentatin B (1) is a cycloartane triterpene isolated from Parthenium argentatum with inhibitory activity on tumor lines. The aim of this study is to investigate the inhibitory effect of 1 and 10 derivatives on the proliferation of a human colon cancer cell line (RKO), their genotoxic effects on human lymphocytes, as well as their potential effect on tumor protein (TP)-p53 and TP73 expression and phosphorylation. Argentatin B was found to induce reduced survival of RKO cells and showed a cytostatic effect. However, it did not induce apoptosis of RKO cells at the concentrations tested. Argentatin B and its derivatives were found to arrest the cell cycle at the G1 phase. The bromine 2 and oxime 6 derivatives were more active than 1. Furthermore, 1 and its bromine (2) and oxime (6) derivatives ind...

BMC Chemistry, 2021

Background Pyrazoles have attracted particular attention due to the diverse biological activities... more Background Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. Results 4,4ʹ-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4ʹ-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized in high to ...

Revista de Medicina y Cine, 2020

Evidence-Based Complementary and Alternative Medicine, 2020

Traditional herbal medicine has become an important alternative in the treatment of various cance... more Traditional herbal medicine has become an important alternative in the treatment of various cancer types, including colon cancer, which represents one of the main health problems around the world. Therefore, the search for new therapies to counteract this disease is very active. Grias neuberthii is an endemic plant located in the Ecuadorian Amazon region, which has been used in traditional medicine for its pharmacological properties, including its ability to inhibit tumor cell growth, although scientific studies are limited. We have analyzed the effect of this plant on two colon carcinoma cell lines, that is, RKO (normal p53) and SW613-B3 (mutated p53) cells. Among several extracts obtained from various parts of G. neuberthii plant, we identified the extract with the greatest cytotoxic potential, derived from the stem bark. The cytotoxic effect was similar on both cell lines, thus indicating that it is independent of the status of p53. However, significant differences were observed ...

Pharmacognosy Journal, 2020

Plants play an important role in health care and are an important source of potentially bioactive... more Plants play an important role in health care and are an important source of potentially bioactive substances 11. The genus Clusia is widely distributed in the tropical and subtropical regions of Central and South America 12. In the species of this genus, a great variety of biological activities have been found: broad-spectrum antimicrobial activity; chemopreventive cancer effects and antioxidant activity 13 ; anti-inflammatory and anti-hepatotoxic activity and inhibitory action of the human immunodeficiency virus (HIV) 14-16 ; and cytotoxic ABSTRACT Introduction: The prevalence of diabetes has increased more rapidly in low and middleincome countries than in high-income countries. Type 2 diabetes mellitus (DM2), which is the most common form of diabetes, is caused by the inefficient use of insulin in the body and is characterized by disrupted insulin action or secretion. Also, oxidative stress plays an important role in the development of disease. The goal of this study is to identify the antioxidant and hypoglycemic properties of Clusia latipes, an endemic species of Central and South America. Methods: The antioxidant and hypoglycemic capacity of the extracts (hexane, ethyl acetate, and methanol) of the leaves and stems of Clusia latipes were evaluated. From the most potent extract, the phytochemical study was carried out and fractionated. Antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), while hypoglycemic capacity was measured by alpha-glucosidase inhibition. Results: The extracts with the highest antioxidant capacity are the extracts with the highest α-glucosidase inhibition activity. Inhibitory activity increased in samples extracted with medium polar (ethyl acetate) and polar (methanol) solvents. Phytochemical screening of these extracts revealed the presence of alkaloids, carbohydrates, flavonoids/xanthones, quinones, saponins, and tannins. The highest α-glucosidase inhibitory activity was detected in the ethyl acetate fraction obtained from leaf methanol extract, with a half-maximal inhibitory concentration (IC 50) value of 0.90 μg/ml. The major constituent isolated from the same fraction was isoquercitrin.

BMC complementary and alternative medicine, Jan 19, 2017

Background: "Horchata" is an herbal mixture infusion consumed in Southern Ecuador; 66% of its pla... more Background: "Horchata" is an herbal mixture infusion consumed in Southern Ecuador; 66% of its plants are antiinflammatory medicinal plant, and 51% are analgesics. Anti-inflammatory substances can prevent carcinogenesis mediated by cytotoxic effects and can prevent DNA damage. The aim of this study was to evaluate the cytotoxicity and apoptotic/antigenotoxic effects of horchata as well as its mechanism. Methods: Nine different varieties of horchata were prepared in the traditional way and then freeze-dried. Phytochemical screening tested for the presence of secondary metabolites using standard procedures and antioxidant activities. The cytotoxic activity was evaluated on cerebral astrocytoma (D-384), prostate cancer (PC-3), breast cancer (MCF-7), colon cancer (RKO), lung cancer (A-549), immortalized Chinese hamster ovary cells (CHO-K1), and human peripheral blood lymphocytes via a MTS assay. The pro-apoptotic effects were evaluated with Anexin V/Propidium Iodide and western blot of Bax, Bcl-2, TP53, and TP73. Induction and reduction of ROS were assessed by fluorimetry. Genotoxic and antigenotoxic effects were evaluated with a comet assay and micronuclei on binucleated cells. Results: Five of nine horchatas had cytotoxic effects against D-384 while not affecting normal cells. These horchatas induce cell death by apoptosis modulated by p53/p73. In CHO-K1 cells, the horchatas decrease the damage induced by hydrogen peroxide and Mitomycin C measured in the comet and micronucleus assay respectively. Conclusions: The IC 50 range of effective horchatas in D-384 was 41 to 122 μg•mL −1. This effect may be related to its use in traditional medicine (brain tonic). On the other hand, immortalized Chinese hamster ovary cells (CHO-K1) and lymphocytes did not show a cytotoxic effect. The most potent horchata induced apoptosis via a p53/p73mediated mechanism. The horchatas present antigenotoxic properties, which may be related to the antioxidant capacity. Future studies on horchata components are necessary to understand the interactions and beneficial properties.

Journal of Ethnobiology and Ethnomedicine, 2017

Background: The "horchata" is a herbal mixture infusion consumed in Southern Ecuador. It remains ... more Background: The "horchata" is a herbal mixture infusion consumed in Southern Ecuador. It remains unknown how vendors group the plant species to sell them at traditional markets. This research documented the following: 1) a list of medicinal plant species sold for the drink; 2) the culturally important medicinal plant species; 3) the agreement among vendors regarding the medicinal plants species and their therapeutic use; and 4) the groups of medicinal plants sold for the preparation of "horchata." Methods: Interviews were made to 185 vendors at 31 traditional markets in Loja province. Bunches of medicinal plants were purchased to identify the species and to prepare voucher specimens. Culturally important medicinal plants species were established with the Fidelity Level (FL) index. Agreement among vendors on the therapeutic use of medicinal plants was measured with the Factor of Informant Consensus (FIC) index. A cluster analysis was made to determine the groups of medicinal plants sold by market vendors to prepare the "horchata" drink. Results: In Loja province, the "horchata" drink is consumed for its therapeutic uses. This study registered 33 families with 58 genera and 71 medicinal plant species, 50 of which are herbs and three are endemic to the Andean highlands of Ecuador. The FL index (46.1-96.3) determined 20 culturally important medicinal plant species. The highest FIC value (1.00) among vendors corresponds to four plant species employed each for a different therapeutic use. The cluster analysis identified a core group of 16 plant species which are essential to the drink and which likely interact to provide wellbeing. Conclusions: The "horchata" is a heritage drink in Loja province. The 71 medicinal plants species registered for this drink is the largest number reported to date, and they have a total of 32 therapeutic uses. The combined results of the FL and FIC indices, the cluster analysis, and the field observations reveal an agreement among vendors on 16 medicinal plant species and their therapeutic use. This core group of plants requires bioactivity and bioassays analyses to determine biomedicine benefits that would be based on their pharmacological properties.

Current Genomics, 2017

Natural compounds from various plants, microorganisms and marine species play an important role i... more Natural compounds from various plants, microorganisms and marine species play an important role in the discovery novel components that can be successfully used in numerous biomedical applications, including anticancer therapeutics. Since uncontrolled and rapid cell division is a hallmark of cancer, unraveling the molecular mechanisms underlying mitosis is key to understanding how various natural compounds might function as inhibitors of cell cycle progression. A number of natural compounds that inhibit the cell cycle arrest have proven effective for killing cancer cells in vitro, in vivo and in clinical settings. Significant advances that have been recently made in the understanding of molecular mechanisms underlying the cell cycle regulation using the chemotherapeutic agents is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to anticancer drugs, especially of natural origin, which inhibit the activities of cyclins and cyclin-dependent kinases, as well as other proteins and enzymes involved in proper regulation of cell cycle leading to controlled cell proliferation.

European Journal of Medicinal Chemistry, 2017

Intestinal parasites delay mental and physical development in children. Infection with these para... more Intestinal parasites delay mental and physical development in children. Infection with these parasites can result in complications during pregnancy and alter the health of newborns, which has long-term effects on educational attainment and economic productivity. The appearance of resistance against classical drug treatments generates interest in the development of new deworming alternatives. We think that research of new plants species may reveal potential antiparasitic compounds. This review is focused on the use of plants and secondary metabolites against intestinal parasites. We discuss the use of plants in traditional medicine and the use of plant secondary metabolites tried in in vitro and in vivo models when available.

Journal of Ethnobiology and Ethnomedicine, 2016

Background: The traditional markets in southern Ecuador and within the Andean region are especial... more Background: The traditional markets in southern Ecuador and within the Andean region are especially important for plant resource trading among local people, even since before Spanish colonization; therefore, ethnobotanical studies are currently necessary and important. These strategic spaces persist for the traditional medicine cultural value reflected in the higher consumption of medicinal plants, which span all socioeconomic levels of rural and urban people. The purpose of this study includes the following: 1) to create a novel list of medicinal plants sold at 33 traditional markets; 2) to establish medicinal plant use agreement amongst vendors with the Factor of Informant Consensus (FIC); and 3) to determine the most sold medicinal plant species using the Fidelity Level (FL). Methods: This study focus on traditional markets ethnobotany utilizes the largest sample of medicinal plants market vendors up to date in Ecuador, interviewing them at 33 traditional markets, located within the Loja province. In order to determine the most sold medicinal plants and their ethnobotanical information, structured questionnaires and personal conversations were conducted with 196 medicinal plant vendors, and voucher specimens were created. Agreement among vendors about the therapeutic use of medicinal plants was measured using the FIC, and the most sold medicinal plant species were assessed with the FL. Results and discussion: This research registered 160 medicinal plant species, grouped in 126 genera and 57 families that were sold in 33 traditional markets. The uses of medicinal plants in southern Ecuador are related to a long history of traditional medicine health practices that has persisted until today as well as high plant diversity. The 53 therapeutic uses recorded were grouped into 12 medical categories that were adapted from the World Health Organization. Three medical categories shared the highest value for FIC = 0.92, which showed a high level of agreement of market vendors for 57 medicinal plant species sold to treat ailments related with digestive, dermatological, and sensorial systems. The FL index determined 11 culturally important medicinal plant species based on the reported uses by 40 or more market vendors. Two medicinal plant species had an FL = 100 %, Matricaria recutita and Gaiadendrum punctatum, used to treat digestive and respiratory systems ailments.

Food and Agricultural Immunology, 2016

Pulverized immature fruits of Annona montana M. are commonly used for biomedical applications, es... more Pulverized immature fruits of Annona montana M. are commonly used for biomedical applications, especially in the treatment of dysentery. The aim of this study was to investigate whether hexane, ethyl acetate or methanol extracts of A. montana M. can be cytotoxic to human tumor cells or exhibit genotoxic effects on normal human cells. The organic extracts were shown to inhibit survival of tumor cells originating from human astrocytoma, breast, colon, lung and prostate cancers. Furthermore, they were found to induce DNA damage in normal human lymphocytes, as shown by comet assay. The genotoxic effects observed suggest that traditional folk medicines prepared from extracts of the immature fruit of A. montana should be used with caution.

Bioorganic & Medicinal Chemistry, 2014

The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the antiinf... more The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the antiinflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED 50 = 1.5 Â 10 À4 mmol/ear) and argentatin A (ED 50 = 2.8 Â 10 À4 mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED 50 = 4.5 Â 10 À4 mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPAinduced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24oic acid, obtained from argentatin A (ED 50 = 1.4 Â 10 À4 mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15 lM doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity.

Tumor Biology, 2014

Cancer remains a public health problem with a high unmet medical demand. However, in recent decad... more Cancer remains a public health problem with a high unmet medical demand. However, in recent decades, the knowledge of several functional molecular and biological traits that distinguish tumor cells from normal cells, known as the hallmarks of cancer as described by Hannahan and Weinberg, has led to new and modern therapeutic approaches against this disease. Most cancer drugs are deliberately developed for specific molecular targets that involve these hallmarks. In this review, we address the currently available cancer drugs and development of new drugs from the perspective of their interaction with these hallmarks as well as the pathways and mechanisms involved.

Medicinal Chemistry Research, 2015

Ecuador is well known for its biodiversity and its ancient richness. This review provides an over... more Ecuador is well known for its biodiversity and its ancient richness. This review provides an overview of Ecuadorian plant species in terms of the ethnobotany and chemistry of natural products in relation to anticancer activity. Plant species were classified into two groups: (a) Ethnomedical species with confirmed antitumor activity and (b) species indigenous to Ecuador with anti-cancer potential. This review shows that there is a great chemical diversity in Ecuadorian plants that can be used for potential antitumor therapeutics, and chemical and biological analysis confirms the biomedical use of the plant-derived compounds as cytotoxic agents for cancer cells.