ABSTRACT
Background: Cancer is a leading cause of death for people worldwide, in addition to the rise in mortality rates attributed to the Covid epidemic. This allows scientists to do additional research. Here, we have selected Integerrimide A, cordy heptapeptide, and Oligotetrapeptide as the three cyclic proteins that will be further studied and investigated in this context.Methods: Docking research was carried out using the protein complexes 1FKB and 1YET, downloaded from the PDB database and used in the docking investigations. Cyclopeptides have been reported to bind molecularly to human HSP90 (Heat shock protein) and FK506. It was possible to locate HSP90 in Protein Data Banks 1YET and 1FKB. HSP90 was retrieved from Protein Data Bank 1YET and 1FKB. Based on these findings, it is possible that the anticancer effects of Int A, Cordy, and Oligo substances could be due to their ability to inhibit the mTOR rapamycin binding domain and the HSP90 Geldanamycin binding domain via the mTOR and mTOR chaperone pathways. During the calculation, there were three stages: system development, energy reduction, and molecular dynamics (also known as molecular dynamics). Each of the three compounds demonstrated a binding affinity for mTOR's Rapamycin binding site that ranged from -6.80 to -9.20 Kcal/mol (FKB12).Results: An inhibition constant Ki of 181.05 nM characterized Cordy A with the highest binding affinity (-9.20 Kcal/mol). Among the three tested compounds, Cordy A was selected for MD simulation. HCT116 and B16F10 cell lines were used to test each compound's anticancer efficacy. Doxorubicin was used as a standard drug. The cytotoxic activity of substances Int A, Cordy A, and Oligo on HCT116 cell lines was found to be 77.65 μM, 145.36 μM, and 175.54 μM when compared to Doxorubicin 48.63 μM, similarly utilizing B16F10 cell lines was found to be 68.63 μM, 127.63 μM, and 139.11 μM to Doxorubicin 45.25 μM.Conclusion: Compound Cordy A was more effective than any other cyclic peptides tested in this investigation.
ABSTRACT
Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.
ABSTRACT
Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds had low toxicities and good absorption and solubility properties. The molecular docking results revealed that the propensity for binding to SARS-CoV-2 main protease is extraordinary. The results are remarkable not only for the binding energy values, which outperform several compounds in prior studies, but also for the number of hydrogen bonds formed. Compound 7a was capable of forming 10 strong hydrogen bonds as well as interact to the protein receptor with a binding energy of -7.79 kcal/mol. Therefore, these compounds should be highlighted in further experimental studies in the context of treating SARS-CoV-2 infection and its effects.
ABSTRACT
Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.
Subject(s)
COVID-19 Drug Treatment , Capsicum , Animals , Antioxidants/pharmacology , Capsaicin/pharmacology , Capsicum/chemistry , Flavonoids , Humans , Oxygen , SARS-CoV-2ABSTRACT
For thousands of years, plant based herbal medicines have been utilized by millions of people all over the world. Plant materials or products are used in different folk/traditional medical systems, such as the Chinese, African and Indian medical systems, like Siddha, Ayurveda, Unani, and Homeopathy. Tinospora cordifolia (TC) is a medicinal plant belonging to the family Menispermaceae. It is a big deciduous, climbing shrub growing prevalently in the tropical part of Indian subcontinent regions such as India, Pakistan, Nepal, Bhutan, Bangladesh and Srilanka, and in Myanmar, and China. Guduchi, Giloy, Shindilkodi, and Amritha are all the common names for this plant. Extracts from different parts of this herbal plant have been used to treat many diseases. In Ayurvedic medicine, extract from this plant is used for preparing "rasayanas", which is known to cure diabetes, skin diseases, allergic conditions, jaundice, cardiovascular diseases, rheumatoid arthritis, poisoning, and microbial infections. T. cordifolia has a many bioactive phytochemicals that have been isolated from its aerial parts and roots. Many bioactive principles have been reported from this plant which belong to various classes like alkaloids, aliphatic compounds, diterpenoid lactones, phenolics, flavonoids, glycosides, sesquiterpenoids, lignans, steroids and polysaccharides. T. cordifolia possesses medicinal properties such as antioxidant, antiallergic, antiinflammatory, antimicrobial, antiviral, antidote, antitumor, antileprotic, antispasmodic, and antidiabetic properties. The present review will provide a comprehensive therapeutic potential of T. cordifolia.
ABSTRACT
Diosmin is the 7-rutinoside of 3 ', 5,7-trihydroxy-4'-methoxyflavone (7-O-rutinoside of diosmetin), and hespheridine is the 7-rutinoside of 3', 5,7-trihydroxy-4'-methoxyflavanone (7 -O-rutinoside hesperetin). Diosmin, is a gray-yellow or pale-yellow, hygroscopic powder, whereas hesperidine is in the form of light-yellow spherocrystals. Diosmin was isolated from fruits of the Citrus genus (C. sinensis, C. limonia), now it is obtained semi-synthetically from natural hesperidin. These flavonoids have, among others: antimicrobial, anti-inflammatory, anti-diabetic, anti-cancer, analgesic, antioxidant and possibly anti-virus activity, that cause COVID-19. The metabolism of diosmin takes place initially in the small intestine and involves demethoxylation and hydrolysis. In contrast, oxidation and conjugation take place in the liver. There is no presence of diosmin and diosmetin in the urine, which are mainly eliminated in the form of glucuronic acid conjugates. The dominant metabolite detected in urine samples is m-hydroxy-phenylpropionic acid, excreted in conjugated form. Diosmin may reduce the aggregation of Red Blood Cells, and thus it is able to reduce blood viscosity. The LD50 of the mixture of 90% diosmin and 10% hesperidin for rats is over 3 g/kg. The tests did not reveal any mutagenic effects or effects on reproductive functions. It also does not pose a significant threat during breast feeding, as it poorly passes into breast milk.
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MicroRNAs have been projected as promising tools for diagnostic and prognostic purposes in cancer. More recently, they have been highlighted as RNA therapeutic targets for cancer therapy. Though miRs perform a generic function of post-transcriptional gene regulation, their utility in RNA therapeutics mostly relies on their biochemical nature and their assembly with other macromolecules. Release of extracellular miRs is broadly categorized into two different compositions, namely exosomal (extracellular vesicles) and non-exosomal. This nature of miRs not only affects the uptake into target cells but also poses a challenge and opportunity for RNA therapeutics in cancer. By virtue of their ability to act as mediators of intercellular communication in the tumor microenvironment, extracellular miRs perform both, depending upon the target cell and target landscape, pro- and anti-tumor functions. Tumor-derived miRs mostly perform pro-tumor functions, whereas host cell- or stroma-derived miRs are involved in anti-tumor activities. This review deals with the recent understanding of exosomal and non-exosomal miRs in the tumor microenvironment, as a tool for pro- and anti-tumor activity and prospective exploit options for cancer therapy.
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Spondias mombin is one of the species belonging to the (Family: Anacardiaceae), its ethnomedicinal uses may be justified through many studies that reported potential pharmacological properties due to its phytochemical compounds. This review aimed at examining the ethnomedicinal uses, phytochemical compounds and pharmacological properties of S. mombin leaf extracts on the African continent, to justify its use in the management and/ or treatment of viral infections and cancers. Electronic databases such as Google Scholar, SciHub, PubMed and Science Direct with search dates between 1999 and 2019 were used. Findings from this review confirm the ethnomedicinal uses, of decoctions and infusions of S. mombin leaf extracts for management diseases such as malaria, sore throat, and inflammation disorders;studies confirmed the presence of phytochemical compounds such as Geraniin, 2-O-Caffeoyl-(+)-allohydroxycitric acid, Quercetin-3-O-beta-D-glucopyranoside and pelandjuaic acid, responsible for the antiviral and chemotherapeutic properties. However, there is a need for bio-assay guided extractions, isolation, identification and characterization of phytochemical compound(s) in the leaf extracts of S. mombin that may be responsible for antiviral and anticancer activity. Investigations of the pharmacological action, in silico and in vitro studies of known and /or newly isolated compounds are warranted in the management and /or treatment of viral infections such as, Severe Acute Respiratory Syndrome Coronavirus 2, and cancers to justify the use of leaf extracts of S. mombin on the African continent for the management of viral infections and or cancer.
ABSTRACT
Taif rose (Rosa damascena Mill) is one of the most important economic products of the Taif Governorate, Saudi Arabia. Cadmium chloride (CdCl2) is a common environmental pollutant that is widely used in industries and essentially induces many toxicities, including hepatotoxicity. In this study, the major compounds in the waste of Taif rose extract (WTR) were identified and chemically and biologically evaluated. GC–MS analysis of WTR indicated the presence of many saturated fatty acids, vitamin E, triterpene, dicarboxylic acid, terpene, linoleic acid, diterpenoid, monoterpenoid, flavonoids, phenylpyrazoles, and calcifediol (vitamin D derivative). The assessment of potential anticancer activity against HepG2 cells proved that WTR had a high cell killing effect with IC50 of 100–150 µg/mL. In addition, WTR successfully induced high cell cycle arrest at G0/G1, S, and G2 phases, significant apoptosis, necrosis, and increased autophagic cell death response in the HepG2 line. For the evaluation of its anti-CdCl2 toxicity, 32 male rats were allocated to four groups: control, CdCl2, WTR, and CdCl2 plus WTR. Hepatic functions and antioxidant biomarkers (SOD, CAT, GRx, GPx, and MDA) were examined. Histological changes and TEM variations in the liver were also investigated to indicate liver status. The results proved that WTR alleviated CdCl2 hepatotoxicity by improving all hepatic vitality markers. In conclusion, WTR could be used as a preventive and therapeutic natural agent for the inhibition of hepatic diseases and the improvement of redox status. Additional in vitro and in vivo studies are warranted.
ABSTRACT
Neem (Azadirachta indica) a member of Meliaceae plays an immense role in human health and disease which is attributed to its composition of Bioactive Secondary Metabolites (BASM). It has been widely used in Indian Traditional Systems of Medicine that includes Ayurveda, Siddha, Unani, Homeopathy and other Folklore Systems of Medicine practiced in the Indian Subcontinent for the treatment and prevention of various diseases. Current global health perspectives and medical practice in the post COVID era has no other way but to seek to merge alternative systems of medicine with evidence-based therapeutic aspects for a better understanding of the metabolic process and its effects in the human body. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-B, PI3K/Akt, Bcl-2, and VEGF. Besides, NEEM plays a vital role in the management of diabetics and its associated long term complication through ROS scavenging and ameliorative potentials to restore oxidative injury/inhibit enzymes linked to. Overall NEEM is considered as GRAS medicinal plant that modulates metabolic inflammations without side effects. Though it has been confirmed that neem and its constituents play role in the scavenging of free radical and prevention of disease pathogenesis, a clear scientific basis of its pharmacoinformatics is still lacking. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the fractions revealed the presence of 62 metabolites.