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  • Open access
  • 14 Reads
Effects of chronic Tamoxifen treatment in the hypothalamic circuitry that regulates female sexual behaviour
Published: 08 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session Posters

Breast cancer (BC) is a disease responsible for high rate of morbidity and death in women. Tamoxifen (TAM) has been used for decades as an anti-estrogen in estrogen-dependent BC treatment while endocrine therapies have improved the clinical outcomes in this disease.

Nevertheless, TAM therapy is still accompanied by a wide spectrum of side effects. By expanding the indications for endocrine therapy, the majority of women diagnosed with BC can be expected to live longer. The increased survival rate leads to increased risk of deleterious side effects associated with TAM treatment. Because nowadays it is offered a 5 years prophylactic TAM therapy to woman with high risk of having BC, the impact of endocrine therapy on the quality of life is extremely important.

Previous studies have shown that TAM inhibits female rodent sexual behavior and women taking TAM complain about diminished libido; however, the mechanisms underlying this event are currently unknown. With the identification of the effects of long-term TAM therapy in the structural and biochemical plasticity of the medial preoptic (MPN) and the ventromedial hypothalamic nuclei (VMN), hypothalamic areas that control the proceptive and the receptive component, respectively, of the female sexual behavior, this study aimed to improve the knowledge about the behavioral outcomes associated with TAM therapy.

TAM was administrated daily, for three months, to normally cycling young female Wistar rats in a dose known to mimic the one used by woman in hormone therapy. In order to identify the effects of TAM in the estrous cyclicity, vaginal lavage was done daily and the uterine weight and estradiol levels were determined upon sacrifice. The brain areas were studied using immunohistochemistry for the detection of the expression of estrogen and progesterone receptors. The results show that TAM inhibits the cycling fluctuation of estradiol and progesterone inducing changes in the expression and co-expression of both receptors in the VMN and MPN suggesting a possible mechanism of action in the inhibition of the sexual response.

  • Open access
  • 28 Reads
Abietane Diterpenoids from Plectranthus spp. as a potential new class of Protein Kinase C Modulators

Cancer is one of the highest causes of death worldwide. Protein kinase C (PKC) is a family of kinases divided into three groups according to their regulatory domain structure and cofactors requirement for activation: classical, novel, and atypical PKCs. Recently, PKC family isoforms have been the focus of intense research, and recognized as therapeutic targets in anticancer drug development [1]. Diterpenoids are commonly found in the Plectranthus spp., and have a widespread spectrum of biological activity, namely anticancer properties [2]. The diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (AHR) isolated from P. grandidentatus displays low cytotoxicity and the basic requirements approaches for the development of pharmaceutical formulations based on AHR as a lead. These AHR features includes an extraction optimization and structural and thermal properties characterization [3]. These features suggests that AHR can be used as a lead for drug development. Considering this, a small library of abietane derivatives was tested for their ability to activate PKC isoforms from classical (alpha, α; beta, β), novel (delta, d; epsilon, e) and atypical (zeta, z) subfamilies, using a previously developed yeast-based screening assay to search for modulators of PKC isoforms [4]. The results obtained revealed potent activators of PKC family proteins, namely: a selective activator of PKCd, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz). The patented diterpenoid RoyBz was prepared using AHR as starting material. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCd-dependent mitochondrial apoptotic pathway involving caspase-3 activation. The results indicate that Roy-Bz targets drug resistant cancer stem cells, in HCT116 colon cancer cells, preventing tumor dissemination and recurrence. Moreover, these findings support a tumor suppressive function of PKCd in colon cancer. Overall, these results point to promising activators of PKCs with high potency and isoform-selectivity that may emerge from the exploitation of this new family of abietane diterpenoids [5]. Molecular docking studies are currently ongoing to further identify new selective abietane diterpenoids as new PKC modulators.

  • Open access
  • 12 Reads
Ethnomedicinal studies on medicinal plants used by people of Rif, Morocco
Published: 09 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Background: Since early times, the people of Morocco use medicinal and aromatic plants as traditional medicine to heal different human ailments. However, little studies have been made in the past to properly document and promote the traditional ethnomedical knowledge.

Objective: This study was carried out in the Rif (North of Morocco), it aimed to establish the catalog of medicinal plants and to identify medicinal and aromatic plant used by the local people to treat diseases, together with the associated ethnomedicinal knowledge.

Material and Methods: The ethnomedical information collected was from 1000 local healers using semi-structured interviews, free listing and focus group. Family importance value (FIV), relative frequency of citation (RFC), plant part value (PPV), fidelity level (FL) and informant consensus factor (ICF) were employed in data analysis. Medicinal and aromatic plant were collected, identified and kept at the natural resources and biodiversity laboratory, Ibn Tofail University, Kenitra.

Results: During the present study 290 medicinal plant species belonging to 74 families has been documented. The most frequent ailments reported were osteoarticular diseases (ICF = 0.9818). The majority of the remedies were prepared from decoction (38.6%). Leaves were the most frequently used plant part (PPV 0.364) and Rosmarinus officinalis L. (RFC = 0.189) was the specie most commonly prescribed by local herbalists.

Conclusions: The results of this study showed the existence of indigenous ethnomedicinal knowledge of medicinal plants in the Moroccan Rif to treat diseases. Further research on phytochemical, pharmacological and toxicological should be considered to discover new drugs from these documented plants.

  • Open access
  • 11 Reads
Assessment of chemical composition and antidiabetic potential of Putranjiva roxburghii twigs
Published: 09 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Background: Putranjiva roxburghii belongs to the Putranjivaceae family and usually grow in India, Nepal, Bangladesh and Sri Lanka. Traditionally, leaves and seeds are used for treating fever, inflammation and pain.

Aim of the study: The objective of the study is to isolate and characterize the chemical constituents from Putranjiva twigs and evaluate its antidiabetic potential.

Methods: The powdered material of twigs extracted with alcohol and partitioned into different fractions. Chemical fingerprint of each fraction was developed by RP-HPLC method. The isolation performed with butanol fraction and two new compounds obtained. The pure compounds assessed for the dose dependent glucose uptake assay on L6 myotubes in Dulbecco modified Eagle medium. Up-regulatory effects of the compounds with insulin and TNF-α expression level have been studied.

Results: The isolation from twigs butanol fraction gave two new compounds-2, 4 dihydroxy-5-(hydroxymethyl) benzoic acid (1) and L-quebrachitol (2) of phenolic and cyclitol class respectively. The up-regulation of glucose uptake of the compounds were comparable with insulin and standard drug metformin.

Conclusion: The results of present study indicate that plant has varied secondary metabolites with potential antidiabetic activity. However, the plant is not well explored and requires scientific validation in detailed in vivo studies and their mode of action.

  • Open access
  • 15 Reads
How drugs interact and stabilize themselves in the vicinity of DNA? A computational quest
Published: 09 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Deoxyribonucleic acid has been a known cellular target for many anticancer agents for several decades. The interaction of drugs with nucleic acid is one of the essential features in pharmacology and plays a significant role to understand the mechanism of drug action and in designing more efficient drugs with lesser side effects.

In the current research work, diarylfurans which were claimed to possess antimicrobial tendencies were studied for their relative binding strengths and stable complex formation tendencies with DNA (PDB Id: 195D). Molecular docking calculations were performed to predict the binding pocket of the drug in the vicinity of DNA and molecular dynamics (MD) were performed to study the interaction dynamics in support of predicted binding mode. Docking revealed that the binding site was AT-rich region, as preferred by minor groove binders. RMSD and RMSF analysis were done from the obtained from MD studies; the former study revealed that ligands remain bound to the preferred binding positions of the DNA without any considerable deviations in its minor groove; however the later revealed the topological structure of DNA remaining intact during the entire course of the simulation, inferring the stability of drug-DNA complexes.

This study describes the properties and dynamics of DNA on the interaction with minor groove binders, taking account of deformation upon binding which can play a significant role in the discovery of new minor groove binders as a regulator of gene expression.

  • Open access
  • 7 Reads
In vitro Screening of alcoholic and hydroalcoholic extracts of Ayurvedic medicinal plants for the management of hyperlipidemia
Published: 09 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Background: In Ayurveda, obesity is regarded as ‘Medoroga’, a disorder of lipid metabolism. Hyperlipidemia is one of the causes of obesity. It is a condition when abnormally high levels of lipids (fatty substances) are found in the blood.

Aim: The objective of the present study is to explore pancreatic lipase inhibitory activity of plants used in Indian system of medicine i.e. Ayurveda.

Method: In the present study, thirty one ‘Lekhenya’ plants were selected from the Ayurveda. Air-dried and finely powdered material (2.0 g) from 31 plants was extracted with ethanol and hydro-alcohol (50:50; v/v) (3 × 10 ml) using cold percolation. The inhibition of pancreatic lipase activity of different plant extracts and orlistat (positive control) was measured in vitro using a spectrophotometric assay.

Results : In vitro lipase inhibition assay showed that six plants, namely Sterosperum servolides (Roxb.) D.C, Prunus cerasoides D. Don, Murraya koenigii L., Putranjiva roxburghii Wall., Andrographis paniculata (Burm. f.) Wall. ex Nees, Ocimum scantum linn, exhibited IC50 values lower than 100 (µg/ml).

Conclusion: The study indicated that lipase inhibition potential of Ayurvedic plants might be useful for the management of obesity, what correlates with ethnopharmacological data on the use of these plants in Indian traditional medicines.

  • Open access
  • 9 Reads
HPLC-based bioactivity profiling for investigation of potent xanthine oxidase inhibitors from Zanthoxylum armatum fruits
Published: 10 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

Background: Zanthoxylum armatum DC (Family Rutaceae) is traditionally used as carminative, as well as for treatment of gout, pain, and inflammation. Because gout and hyperuricemia are caused by accumulation of uric acid, xanthine oxidase inhibitors may play a role in those dysfunctions.

Objective: Investigation of xanthine oxidase (XO) inhibitory activity (in vitro) of Z. armatum fruits extracts and fractionation of bioactive extracts for separation and isolation of bioactive compounds by HPLC.

Materials and methods: Powdered fruits of Z. armatum were extracted and evaluated for xanthine oxidase inhibitory activity. An efficient method based on bioactivity guided fractionation using preparative-HPLC was used to separate and evaluate the bioactive compounds from ethyl acetate extract. Solvent system methanol: water (65:35, v/v) was used for the isocratic method of p-HPLC and seven fractions of 5 mL each were collected. Then the active fractions were evaluated for XOI activity and compounds were isolated by peak-resolved manner.

Results: The ethyl acetate extract shows the most significant effect on XO activity (IC50 115.69µM) and XO inhibitory activity of isolated marker chemical was ranging from 5.62 to 41.21 µM.

Conclusion: It is concluded that Z. armatum possesses a significant inhibitory effect against the xanthine oxidase enzyme. Therefor fruits of Z. armatum may lead potential treatment of hyperuricemia.

  • Open access
  • 15 Reads
Synthesis, antibacterial and antifungal studies of cobalt(II) complexes of (2E)-2-(2-hydroxy-3-methoxybenzalidene)hydrazinecarbo(thio)amides
Published: 10 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session Posters

In the present work, six new cobalt(II) complexes (1-6) of (E)-2-(2-hydroxy-3-methoxybenzylidene)-N4-methylhydrazinecarbothioamide (HL1), (E)-2-(2-hydroxy-3-methoxybenzylidene)-hydrazinecarbothioamide (HL2) and (E)-2-(2-hydroxy-3-methoxybenzylidene)-hydrazinecarboxamide (HL3), have been synthesized and characterized. The FT-IR spectral data suggested the attachment of cobalt(II) ion to the Schiff’s base ligand moiety through the azomethine nitrogen, thioketonic sulfur and phenolic-O atom. The synthesized complexes 1-6 were tested for their antibacterial activities against two gram-positive bacteria (Bacillus subtilis and Escherichia coli) and two gram-negative bacteria (Pseudomonas aeruginosa and Staphylococcus aureus) and also screened for their antifungal activity against Aspergillus Niger and Candida Albicans. These complexes showed moderate to considerable effect on bacteria strains, whereas they showed moderate effect on fungal strains.

  • Open access
  • 9 Reads
Photodynamic therapy on a human lung cancer cell line a549 with new bodipy photosensitizers
Published: 11 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session Posters

Lung cancer is the most incident and the deadliest cancer for both men and women. Therefore, the need for new and more effective therapies with fewer side effects is a concern. Photodynamic Therapy (PDT) relies on the administration of a photosensitizer that is subsequently activated by irradiation with light of appropriate wavelength. As a result, reactive oxygen species (ROS) are produced leading to cell death. PDT use in the treatment of cancer is still limited, due to the low number of new approved drugs. In light with this, this work aims to develop new photosensitizers for PDT. As an alternative class of the porphyrin-based photosensitizers, two compounds of the family of the boron−dipyrromethenes (BODIPY) have been synthesized and evaluated on the human lung cancer cell line A549. In this study, we used the MTT and SRB assays to assess the cytotoxicity of the compounds with concentrations ranging from 0,1 to 50 μM. Both compounds are photocytotoxics at the higher concentration studied. The most effective compound in the photocytotoxicity studies was the BODIPY 2 when used in a concentration of 10 and 50 µM. These promising results uphold further studies.

  • Open access
  • 26 Reads
Repurposing Common Food Additives (Benzo Derivatives) As New Anti-parasitic Agents
Published: 11 November 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

This study examined the anti-protozoal effects of selected benzo derivatives, namely ten gallic acid (GA) alkyl esters (viz., benzoic acid analogs) and twenty-three benzaldehyde analogs, against six different anaerobic human protozoal pathogens- - Trichomonas vaginalis, Tritrichomonas foetus, Tritrichomonas foetus-like, Giardia lamblia, Entamoeba histolytica, and Naegleria fowleri. The efficacy of benzaldehyde and gallate (3,4,5-trihydroxybenzoic acid) analogs were investigated in two respects: (1) changing types of side chains and their positions on the benzaldehyde ring [structure–activity relationships (SAR)]; and, (2) changing lengths of alkyl chains esterified with the carboxyl group on gallate. Results of parasite growth inhibition assays indicated that benzo derivatives could be further developed as potent anti-protozoal drug candidates/leads, where GA having longer alkyl chains exhibited higher anti-protozoal activity than compounds with shorter alkyl chains or all benzaldehyde analogs tested. The chemical libraries were also screened against common human microbiome bacteria and no detectable inhibition was observed. Structure-activity relationships and their implications for new drug discovery against these sexually-transmitted, water-borne, and food- borne parasites are discussed.

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