Momordica charantia and breast cancer: An in silico approach

2020 ◽  
Vol 19 (06) ◽  
pp. 2050015
Author(s):  
Malênia Oliveira dos Santos Coelho ◽  
Caroline de Almeida Berbert ◽  
Leonardo Luiz Borges
Keyword(s):  
Breast Cancer ◽  
Phenolic Compounds ◽  
In Silico ◽  
Biological Activities ◽  
Pharmacophore Modeling ◽  
Momordica Charantia ◽  
Ovarian Cancers ◽  
Potential Efficacy

Momordica charantia, known as “São Caetano Melon”, is a medicinal plant popularly used for its antitumor, anticarcinogenic, hypoglycemic, and other properties. Studies in mice have demonstrated its activity in vivo against breast, prostate, and ovarian cancers. In vitro studies have also indicated potential efficacy against cervical solid tumors, and breast cancer. In these studies, we sought to evaluate these putative activities. Our methods included use of in silico tools to assess predicted biological activities, pharmacodynamics, and toxicity. We also performed docking and pharmacophore modeling studies. We found phenolic compounds, flavonoids, alkaloids, and triterpenes. Four flavonoids possess predicted anticarcinogenic activity, and affinity for estrogen receptors. Quercetin was selected for the study because it is the most prevalent representative of its class.

Isolation of hydroxytyrosol from olive leaves extract, radioiodination and investigation of bioaffinity using in vivo/in vitro methods

2013 ◽  
Vol 101 (9) ◽  
pp. 585-593 ◽  
Author(s):  
M. Ozkan ◽  
F. Z. Biber Muftuler ◽  
A. Yurt Kilcar ◽  
E. I. Medine ◽  
P. Unak
Keyword(s):  
Small Intestine ◽  
Phenolic Compounds ◽  
Biological Activities ◽  
In Vivo Studies ◽  
Flavonoid Content ◽  
Olive Leaves ◽  
In Vitro Methods ◽  
Extraction And Purification

Summary It is known that medicinal plants like olive have biological activities due to their flavonoid content such as olueropein, tyrosol, hydroxytyrosol etc. In current study, hydroxytrosol (HT) which is one of the major phenolic compounds in olive, olive leaves and olive oil, was isolated after methanol extraction and purification of olive leaves which are grown in the northern Anatolia region of Turkey. The isolated HT was radiolabeled with 131I (131I-HT) and the bioaffinity of this radiolabeled component of olive leaves extract was investigated by using in vivo/in vitro methods. It was found that HT could be radiolabeled with 131I in yields of 95.6±4.4% (n = 8), and in vivo studies showed that 131I-HT is taken up by urinary bladder, stomach, small intestine, large intestine, breast and prostate. Significant incorporation of activity was observed in cell lines via in vitro studies.

In-silico Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Novel Isoxazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer

2019 ◽  
Vol 11 (2) ◽  
pp. 118-128 ◽  
Author(s):  
Rajagopal Kalirajan ◽  
Arumugasamy Pandiselvi ◽  
Byran Gowramma ◽  
Pandiyan Balachandran
Keyword(s):  
Breast Cancer ◽  
Free Energy ◽  
In Silico ◽  
Therapeutic Potential ◽  
Binding Free Energy ◽  
Breast Cancers ◽  
Molecular Docking Study ◽  
In Silico Admet

Background: Human Epidermal development factor Receptor-2 (HER2) is a membrane tyrosine kinase which is overexpressed and gene amplified in human breast cancers. HER2 amplification and overexpression have been linked to important tumor cell proliferation and survival pathways for 20% of instances of breast cancer. 9-aminoacridines are significant DNA-intercalating agents because of their antiproliferative properties. Objective: Some novel isoxazole substituted 9-anilinoacridines(1a-z) were designed by in-silico technique for their HER2 inhibitory activity. Docking investigations of compounds 1a-z are performed against HER2 (PDB id-3PP0) by using Schrodinger suit 2016-2. Methods: Molecular docking study for the designed molecules 1a-z are performed by Glide module, in-silico ADMET screening by QikProp module and binding free energy by Prime-MMGBSA module of Schrodinger suit. The binding affinity of designed molecules 1a-z towards HER2 was chosen based on GLIDE score. Results: Many compounds showed good hydrophobic communications and hydrogen bonding associations to hinder HER2. The compounds 1a-z, aside from 1z have significant Glide scores in the scope of - 4.91 to - 10.59 when compared with the standard Ethacridine (- 4.23) and Tamoxifen (- 3.78). The in-silico ADMET properties are inside the suggested about drug likeness. MM-GBSA binding of the most intense inhibitor is positive. Conclusion: The outcomes reveal that this study provides evidence for the consideration of isoxazole substituted 9-aminoacridine derivatives as potential HER2 inhibitors. The compounds, 1s,x,v,a,j,r with significant Glide scores may produce significant anti breast cancer activity and further in vitro and in vivo investigations may prove their therapeutic potential.

scholarly journals ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sara Charmsaz ◽  
Ben Doherty ◽  
Sinéad Cocchiglia ◽  
Damir Varešlija ◽  
Attilio Marino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
In Silico ◽  
Ex Vivo ◽  
Metastatic Breast ◽  
Peptide Mimetic ◽  
Breast Cancer Brain Metastasis

Abstract Background Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood–brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. Methods Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target’s natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis. Results Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis. Conclusion ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.

scholarly journals Investigation of biological activities of Colocasia gigantea Hook.f. leaves and PASS prediction, in silico molecular docking with ADME/T analysis of its isolated bioactive compounds

2020 ◽  
Author(s):  
Safaet Alam ◽  
Nazim Uddin Emon ◽  
Mohammad A. Rashid ◽  
Mohammad Arman ◽  
Mohammad Rashedul Haque
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
In Silico ◽  
Castor Oil ◽  
Biological Activities ◽  
Kappa Opioid Receptor ◽  
Soluble Extract ◽  
Docking Score

AbstractBackgroundColocasia gigantea is locally named as kochu and also better known due to its various healing power. This research is to investigate the antidiarrheal, antimicrobial, and antioxidant possibilities of the methanol soluble extract of Colocasia gigantea.MethodsAntidiarrheal investigation was performed by using in vivo castor oil induced diarrheal method where as in vitro antimicrobial and antioxidant investigation have been implemented by disc diffusion and DPPH scavenging method respectively. Moreover, in silico studies were followed by molecular docking analysis of several secondary metabolites were appraised with Schrödinger-Maestro v 11.1.ResultsThe induction of plant extract (200 and 400 mg/kg, b.w, p.o), the castor oil mediated diarrhea has been minimized 19.05 % (p < 0.05) and 42.86 % (p < 0.001) respectively. The methanolic extract of C. gigantea showed mild sensitivity against almost all the tested strains but it shows high consistency of phenolic content and furthermore yielded 67.68 μg/mL of IC50 value in the DPPH test. The higher and lower binding affinity was shown in beta-amyrin and monoglyceryl stearic acid against the kappa-opioid receptor (PDB ID: 4DJH) with a docking score of -3.28 kcal/mol and -6.64 kcal/mol respectively. In the antimicrobial investigation, Penduletin and Beta-Amyrin showed the highest and lowest binding affinity against the selected receptors with the docking score of -8.27 kcal/mol and -1.66 kcal/mol respectively.ConclusionThe results of our scientific research reflect that the methanol soluble extract of C. gigantea is safe which may provide possibilities of alleviation of diarrhea and as a potential wellspring of antioxidants which can be considered as an alternate source for exploration of new medicinal products.

scholarly journals Triazine Derivative as Putative Candidate for the Reduction of Hormone-Positive Breast Tumor: In Silico, Pharmacological, and Toxicological Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Tayyab Imtiaz ◽  
Fareeha Anwar ◽  
Uzma Saleem ◽  
Bashir Ahmad ◽  
Sundas Hira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tumor ◽  
In Silico ◽  
Enzyme Level ◽  
Saline Group ◽  
Female Rats ◽  
Beneficial Effects ◽  
Group I

Background and objectives: Breast cancer is a heterogeneous disease that poses the highest incidence of morbidity among women and presents many treatment challenges. In search of novel breast cancer therapies, several triazine derivatives have been developed for their potential chemotherapeutic activity. This study aims to evaluate the N-nitroso-N-methyl urea (NMU)–induced anti–mammary gland tumor activity of 2,4,6 (O-nitrophenyl amino) 1,3,5-triazine (O-NPAT).Methods: The in silico modeling and in vitro cytotoxicity assay were performed to strengthen the research hypothesis. For in vivo experimentation, 30 female rats were divided into five groups. Group I (normal control) received normal saline. Group II (disease control) received NMU (50 mg/kg). Group III (standard control) was treated with tamoxifen (5 mg/kg). Groups IV and V received O-NPAT at a dose level of 30 and 60 mg/kg, respectively. For tumor induction, 3 intraperitoneal doses of NMU were given at a 3-week interval, whereas all treatment compounds were administered orally for 14 consecutive days. Biochemical and oxidative stress markers were estimated for all experimental animals. DNA strand breakage alongside inflammatory markers was also measured for the analysis of inflammation. The hormonal profile of progesterone and estrogen was also estimated.Results: The test compound presented a significant reduction in organ weight and restored the hepatic and renal enzymes. O-NPAT treatments enhanced the antioxidant enzyme level of catalase (CAT), superoxide dismutase (SOD), and total sulfhydryl (TSH), with a highly significant reduction in lactate dehydrogenase (LDH) and lipid peroxidation. Also, the decrease in fragmented DNA, hormonal levels (estradiol and progesterone), and inflammatory cytokines (IL-6 and TNF-α) justified the dosage efficacy further supported by histopathological findings.Conclusion: All results indicated the anti–breast tumor activity of O-NPAT and presented its possibility of exploitation for beneficial effects in breast cancer treatment.

scholarly journals Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 2001 ◽  
Author(s):  
Ana Karković Marković ◽  
Jelena Torić ◽  
Monika Barbarić ◽  
Cvijeta Jakobušić Brala
Keyword(s):  
Phenolic Compounds ◽  
Olive Oil ◽  
Biological Activities ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Endocrine Effects ◽  
Pharmacological Potential ◽  
A Minor

The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as reduced incidence of different chronic diseases and prolonged longevity. Although olive oil polyphenols present a minor fraction in the composition of olive oil, they seem to be of great importance when it comes to the health benefits, and interest in their biological and potential therapeutic effects is huge. There is a growing body of in vitro and in vivo studies, as well as intervention-based clinical trials, revealing new aspects of already known and many new, previously unknown activities and health effects of these compounds. This review summarizes recent findings regarding biological activities, metabolism and bioavailability of the major olive oil phenolic compounds—hydroxytyrosol, tyrosol, oleuropein, oleocanthal and oleacein—the most important being their antiatherogenic, cardioprotective, anticancer, neuroprotective and endocrine effects. The evidence presented in the review concludes that these phenolic compounds have great pharmacological potential, however, further studies are still required.

scholarly journals Pharmacophore based drug designing of COL7A1; The causative gene of Dystrophic Epidermolysis Bullosa

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Yasra Fatima ◽  
Muhammad Aqib Shabbir ◽  
Noor-ul-Ain ◽  
Syeda Izma Makhdoom ◽  
Hamza Saleem-ur-Rehman ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
In Silico ◽  
Genetic Disorder ◽  
3D Structure ◽  
Pharmacophore Modeling ◽  
Chain Gene ◽  
Causative Gene ◽  
Dystrophic Epidermolysis Bullosa

Epidermolysis Bullosa is a rare genetic disorder that causes skin fragility, trauma induced dissociations of the skin, and painful wound growth. More than 20 types of genes are involved in causing EB as it is a polygenic disease and each gene is involved in a different subtype of EB. Dystrophic Epidermolysis Bullosa (DEB) is one of the subtypes of EB caused by mutations in the COL7A1 (Collagen Type VII Alpha 1 Chain) gene and it affects people from all racial backgrounds. No drug is available for DEB in the market yet. So, it is the need of the hour to come up with a potential inhibitor that could inhibit the faulty protein of COL7A1 gene. Different exons of COL7A1 have been analyzed and exon no 70 to 75 has been selected which were important for mutational point of view. The mutations in it have been identified and verified using various In-silico tools. The 3D structure of the protein has been retrieved using specific exons which were edited and mutations were introduced in it and it was further checked to analyze its stability, toxicity and solubility of the protein. The inhibitors of COL7A1 have been formed using CAAD techniques (pharmacophore modeling) and the best inhibitor of COL7A1 has been further checked to determine its drug-likeness, solubility, its toxicity, and various physiochemical properties. The constructed inhibitor was found to have the best docking results and found to have good ADMET properties. The developed inhibitor construct showing promising results In-silico and it will also show good results if it would be tested in-vitro and in-vivo. Thus, it would be a breakthrough to treat DEB using this inhibitor if this inhibitor is constructed and further tested in-vitro.

In vivo, in vitro and in silico anticancer investigation of fullerene C60 on DMBA induced breast cancer in rats

Life Sciences ◽  
2022 ◽  
pp. 120281
Author(s):  
Seda Beyaz ◽  
Abdullah Aslan ◽  
Ozlem Gok ◽  
Harun Uslu ◽  
Can Ali Agca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Fullerene C60

1,3,4-Thiadiazolo (3,2-Α) Pyrimidine-6-Carbonitrile Scaffold as PARP1 Inhibitors.

2020 ◽  
Vol 21 ◽  
Author(s):  
Elizabeth Eldhose ◽  
Kaviarasan Lakshmanan ◽  
Praveen T. Krishnamurthy ◽  
Kalirajan Rajagopal ◽  
Manal Mohammed ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Activities ◽  
Docking Study ◽  
Binding Mode ◽  
Oral Toxicity ◽  
Standard Drug ◽  
In Silico Docking

Background: 1,3,4-thiadiazolo pyrimidine is a lead molécule which is versatile for a wide variety of biological activities and in continuation of our interest in establishing some novel heterocyclic compounds for antitumor activity. Objective: The objective of the study was to synthesize series of 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] - [1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivative and evaluated for their possible in vitro and in vivo anticancer activity. Methods: Herein we report the synthetic scheme which was followed for the preparation of a series of title compounds B1- B9 is outlined in the scheme 1. The intermediate 5-[(naphthalen-2- yloxy)methyl]-1,3,4-thiadiazolo-2-amine was prepared by heating 2-naphthoxyacetic acid and thiosemicarbazide in presence of phosphoryl chloride at a temperature of 65 - 750C. The obtained compound reacted with malononitrile and appropriate amount of aromatic and heteroaromatic aldehydes in refluxing ethanol yielded 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives (B1 – B9). The purity of synthesized compounds ensured by various spectral analysis. Results: In in-silico molecular docking studies compounds B3 and B9 show binding affinity like known PARP1 inhibitor olaparib. The cellular evaluation indicates that the anticancer activity of compounds B1, B3, B9 is significant when compared to standard drug (olaparib) against MDA-MB-232 cell line and compounds B3, B6, B7 are most active against MCF-7 cell lines. The most active compound B3 was subjected to acute oral toxicity studies by OECD 423 guidelines and in-vivo anti-cancer studies were carried out using DMBA induced model. Conclusion: The in-silico docking study of the newly synthesized compounds were performed, the results showed good binding mode in the active site of PARP1 enzyme. In-silico ADME properties of synthesized compounds were also studied and showed good drug like properties.

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