Main Biological Target Research Articles

CBD Versus CBDP: Comparing In Vitro Receptor-Binding Activities.

Phytocannabinoids with seven-carbon alkyl chains (phorols) have gained a lot of attention, as they are commonly believed to be more potent versions of typical cannabinoids with shorter alkyl chains. At the time of this article, cannabidiphorol (CBDP) and tetrahydrocannabiphorol (THCP) can both be purchased in the North American market, even though their biological activities are nearly unknown. To investigate their relative potency, we conducted in vitro receptor-binding experiments with CBDP (cannabinoid CB1/CB2 receptor antagonism, serotonin 5HT-1A agonism, dopamine D2S (short form) agonism, and mu-opioid negative allosteric modulation) and compared the observed activity with that of CBD. To our knowledge, this is the first publication to investigate CBDP's receptor activity in vitro. A similar activity profile was observed for both CBD and CBDP, with the only notable difference at the CB2 receptor. Contrary to common expectations, CBD was found to be a slightly more potent CB2 antagonist than CBDP (p < 0.05). At the highest tested concentration, CBD demonstrated antagonist activity with a 33% maximum response of SR144528 (selective CB2 antagonist/inverse agonist). CBDP at the same concentration produced a weaker antagonist activity. A radioligand binding assay revealed that among cannabinoid and serotonin receptors, CB2 is likely the main biological target of CBDP. However, both CBD and CBDP were found to be significantly less potent than SR144528. The interaction of CBDP with the mu-opioid receptor (MOR) produced unexpected results. Although the cannabidiol family is considered to be a set of negative allosteric modulators (NAMs) of opioid receptors, we observed a significant increase in met-enkephalin-induced mu-opioid internalization when cells were incubated with 3 µM of CBDP and 1 µM met-enkephalin, a type of activity expected from positive allosteric modulators (PAMs). To provide a structural explanation for the observed PAM effect, we conducted molecular docking simulations. These simulations revealed the co-binding potential of CBDP (or CBD) and met-enkephalin to the MOR.

Evaluation of mitochondrial stress following ultraviolet radiation and 5G radiofrequency field exposure in human skin cells.

Whether human cells are impacted by environmental electromagnetic fields (EMF) is still a matter of debate. With the deployment of the fifth generation (5G) of mobile communication technologies, the carrier frequency is increasing and the human skin becomes the main biological target. Here, we evaluated the impact of 5G-modulated 3.5 GHz radiofrequency (RF) EMF on mitochondrial stress in human fibroblasts and keratinocytes that were exposed for 24 h at specific absorption rateof 0.25, 1, and 4 W/kg. We assessed cell viability, mitochondrial reactive oxygen species(ROS) production, and membrane polarization. Knowing that human skin is the main target of environmental ultraviolet (UV), using the same read-out, we investigated whether subsequent exposure to 5G signal could alter the capacity of UV-B to damage skin cells. We found a statistically significant reduction in mitochondrial ROS concentration in fibroblasts exposed to 5G signal at 1 W/kg. On the contrary, the RF exposure slightly but statistically significantly enhanced the effects of UV-B radiation specifically in keratinocytes at 0.25 and 1 W/kg. No effect was found on mitochondrial membrane potential or apoptosis in any cell types or exposure conditions suggesting that the type and amplitude of the observed effects are very punctual.

Integrating network pharmacology and experimental validation to decipher the mechanism of action of Jingfang Granule in the treatment of viral myocarditis.

This study investigated the mechanisms of Jingfang Granule (JFG) in viral myocarditis (VMC) treatment via network pharmacology-based approach combined with molecular docking and validated the results through in vitro and in vivo experiments. The chemical composition of JFG and its therapeutic targets was queried in Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The targets related to VMC were retrieved from the disease database, and the overlapping targets were screened. Based on the STRING database, a protein-protein interaction network was constructed. Cytoscape software was used to construct the "component-target-disease" interaction network for visualization. GO and KEGG pathway enrichment analyses were performed using Metascape data. Molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software programs. The target genes were further verified in vitro and in vivo. JFG contains 88 active components. The main biological targets of JFG in VMC include quercetin, luteolin, and kaempferol. The molecular docking results showed that the three key targets showed strong binding properties with both the height components of the molecular docking interaction energies. The results of experimental verification results showed that JFG may be used to treat VMC mainly by down-regulating inflammatory factors TNF-α and NF-κB and inhibiting myocardial apoptosis. The results support the network pharmacological data. JFG reduces myocardial inflammation and myocardial cell apoptosis in VMC and protects myocardial tissue.

Marine Natural Products as Innovative Cosmetic Ingredients.

Over the course of the last 20 years, numerous studies have identified the benefits of an array of marine natural ingredients for cosmetic purposes, as they present unique characteristics not found in terrestrial organisms. Consequently, several marine-based ingredients and bioactive compounds are under development, used or considered for skin care and cosmetics. Despite the multitude of cosmetics based on marine sources, only a small proportion of their full potential has been exploited. Many cosmetic industries have turned their attention to the sea to obtain innovative marine-derived compounds for cosmetics, but further research is needed to determine and elucidate the benefits. This review gathers information on the main biological targets for cosmetic ingredients, different classes of marine natural products of interest for cosmetic applications, and the organisms from which such products can be sourced. Although organisms from different phyla present different and varied bioactivities, the algae phylum seems to be the most promising for cosmetic applications, presenting compounds of many classes. In fact, some of these compounds present higher bioactivities than their commercialized counterparts, demonstrating the potential presented by marine-derived compounds for cosmetic applications (i.e., Mycosporine-like amino acids and terpenoids' antioxidant activity). This review also summarizes the major challenges and opportunities faced by marine-derived cosmetic ingredients to successfully reach the market. As a future perspective, we consider that fruitful cooperation among academics and cosmetic industries could lead to a more sustainable market through responsible sourcing of ingredients, implementing ecological manufacturing processes, and experimenting with inventive recycling and reuse programs.

Modulation of GABAA receptors and of GABAergic synapses by the natural alkaloid gelsemine.

The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABAA receptors (GABAARs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABAARs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABAARs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABAARs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABAARs but support a role of GABAARs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system.

Early Metabolomic Markers of Acute Low-Dose Exposure to Uranium in Rats.

Changes in metabolomics over time were studied in rats to identify early biomarkers and highlight the main metabolic pathways that are significantly altered in the period immediately following acute low-dose uranium exposure. A dose response relationship study was established from urine and plasma samples collected periodically over 9 months after the exposure of young adult male rats to uranyl nitrate. LC-MS and biostatistical analysis were used to identify early discriminant metabolites. As expected, low doses of uranium lead to time-based non-toxic biological effects, which can be used to identify early and delayed markers of exposure in both urine and plasma samples. A combination of surrogate markers for uranium exposure was validated from the most discriminant early markers for making effective predictions. N-methyl-nicotinamide, kynurenic acid, serotonin, tryptophan, tryptamine, and indole acetic acid associated with the nicotinate–nicotinamide and tryptophan pathway seem to be one of the main biological targets, as shown previously for chronic contaminations and completed, among others, by betaine metabolism. This study can be considered as a proof of concept for the relevance of metabolomics in the field of low-dose internal contamination by uranium, for the development of predictive diagnostic tests usable for radiotoxicological monitoring.

Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine.

Drug misuse is a significant social and public health problem worldwide. Misused substances exert their neurobehavioural effects through changing neural signalling within the brain, many of them leading to substance dependence and addiction in the longer term. Among drugs with addictive liability, there are illicit classical stimulants such as cocaine and amphetamine, and their more recently available counterparts known as novel psychoactive substances (NPS). Stimulants normally increase dopamine availability in the brain, including the pathway implicated in reward-related behaviour. This pattern is observed in both animal and human brain. The main biological target of stimulants, both classical and NPS, is the dopamine transporter (DAT) implicated in the dopamine-enhancing effects of these drugs. This article aims at reviewing research on the molecular mechanisms underpinning the interactions between stimulant NPS, such as benzofurans, cathinones or piperidine derivatives and DAT, to achieve a greater understanding of the core phenomena that decide about the addictive potential of stimulant NPS. As the methodology is essential in the process of experimental research in this area, we review the applications of in vitro, in vivo and in silico approaches. The latter, including molecular dynamics, attracts the focus of the present review as the method of choice in molecular and atomistic investigations of the mechanisms of addiction of stimulant NPS. Research of this kind is of interest to not only scientists but also health professionals as updated knowledge of NPS, their modes of action and health risks, is needed to tackle the challenges posed by NPS misuse.

A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine.

Osteoarthritis (OA) is a multifaceted musculoskeletal disorder, with a high prevalence worldwide. Articular cartilage and synovial membrane are among the main biological targets in the OA microenvironment. Gaining more knowledge on the accuracy of preclinical in vitro OA models could open innovative avenues in regenerative medicine to bridge major gaps, especially in translation from animals to humans. Our methodological approach entailed searches on Scopus, the Web of Science Core Collection, and EMBASE databases to select the most relevant preclinical in vitro models for studying OA. Predicting the biological response of regenerative strategies requires developing relevant preclinical models able to mimic the OA milieu influencing tissue responses and organ complexity. In this light, standard 2D culture models lack critical properties beyond cell biology, while animal models suffer from several limitations due to species differences. In the literature, most of the in vitro models only recapitulate a tissue compartment, by providing fragmented results. Biotechnological advances may enable scientists to generate new in vitro models that combine easy manipulation and organ complexity. Here, we review the state-of-the-art of preclinical in vitro models in OA and outline how the different preclinical systems (inflammatory/biomechanical/microfluidic models) may be valid tools in regenerative medicine, describing their pros and cons. We then discuss the prospects of specific and combinatorial models to predict biological responses following regenerative approaches focusing on mesenchymal stromal cells (MSCs)-based therapies to reduce animal testing.

Molecular Modelling Study of Heteroarylamide/Sulfonamide Compounds with Antitrypanosomal Activity

According to the World Health Organization (WHO), Chagas disease (CD), whose etiological agent is the Trypanosoma cruzi (T. cruzi) parasite, affects about eight million people, mainly in Latin America. The cruzain enzyme is highlighted among the main biological targets, since it is the most abundant of the cysteine protease class from T. cruzi and is involved in the entire life cycle of the parasite, essential in regulating the interaction between parasite and host. The drugs available for the treatment of CD usually have strong side effects, and the nitro(triazole/imidazole)-based heteroarylamide/sulfonamide compounds (HA/S) emerge with high antitrypanosomal potential. In this study, the quantitative structure-activity relationship (QSAR) were built using partial least squares (PLS) regression, and the results were robust and adequate for predicting and proposing five new derivatives according to the statistical parameters. The docking results suggest that the best-scored HA/S derivatives showed hydrogen bonds with the residuals that comprise the catalytic region of the enzyme. The molecular dynamics (MD) simulations, performed with different methods, revealed the strong stability of the compound obtained by the QSAR model of this study, in addition to a better binding free energy value than the HA/S obtained from literature.

Therapeutic approaches against coronaviruses acute respiratory syndrome.

Coronaviruses represent global health threat. In this century, they have already caused two epidemics and one serious pandemic. Although, at present, there are no approved drugs and therapies for the treatment and prevention of human coronaviruses, several agents, FDA‐approved, and preclinical, have shown in vitro and/or in vivo antiviral activity. An in‐depth analysis of the current situation leads to the identification of several potential drugs that could have an impact on the fight against coronaviruses infections. In this review, we discuss the virology of human coronaviruses highlighting the main biological targets and summarize the current state‐of‐the‐art of possible therapeutic options to inhibit coronaviruses infections. We mostly focus on FDA‐approved and preclinical drugs targeting viral conserved elements.

Mechanisms of Phorbol Ester Toxicity, Determined by Molecular Modelling

Phorbol esters are toxic phytochemicals, whose main biological target is protein kinase C. They bind irreversibly to the protein, causing cell damage. Using computer modelling, we have determined, for the first time, features and mechanisms that lead to the toxicity of phorbol esters.&#x0D; Protein kinase C – delta (PKC-δ) was used as a target protein in computational docking studies with phorbol esters that differ in molecular structure. Binding conformations and stability of ester linkages were analyzed to evaluate their relationship with experimental observations. Results show that an active phorbol ester must exhibit two features: interaction with specific amino acid residues at the binding site and covering the area with a hydrophobic surface. Toxicity of an active phorbol ester is inversely proportional to the intrinsic reactivity of the ester linkage. Phorbol esters bearing free acid chains can directly activate PKC-δ but jatropha phorbol esters are restricted by their acid-moiety ring formations, suggesting similar mechanism of interaction with other phorbol-ester protein targets.

Association of OPRM1 Functional Coding Variant With Opioid Use Disorder

With the current opioid crisis, it is important to improve understanding of the biological mechanisms of opioid use disorder (OUD). To detect genetic risk variants for OUD and determine genetic correlations and causal association with OUD and other traits. A genome-wide association study of electronic health record-defined OUD in the Million Veteran Program sample was conducted, comprising 8529 affected European American individuals and 71 200 opioid-exposed European American controls (defined by electronic health record trajectory analysis) and 4032 affected African American individuals and 26 029 opioid-exposed African American controls. Participants were enrolled from January 10, 2011, to May 21, 2018, with electronic health record data for OUD diagnosis from October 1, 1999, to February 7, 2018. Million Veteran Program results and additional OUD case-control genome-wide association study results from the Yale-Penn and Study of Addiction: Genetics and Environment samples were meta-analyzed (total numbers: European American individuals, 10 544 OUD cases and 72 163 opioid-exposed controls; African American individuals, 5212 cases and 26 876 controls). Data on Yale-Penn participants were collected from February 14, 1999, to April 1, 2017, and data on Study of Addiction: Genetics and Environment participants were collected from 1990 to 2007. The key result was replicated in 2 independent cohorts: proxy-phenotype buprenorphine treatment in the UK Biobank and newly genotyped Yale-Penn participants. Genetic correlations between OUD and other traits were tested, and mendelian randomization analysis was conducted to identify potential causal associations. Main outcomes were International Classification of Diseases, Ninth Revision-diagnosed OUD or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision-diagnosed OUD (Million Veteran Program), and DSM-IV-defined opioid dependence (Yale-Penn and Study of Addiction: Genetics and Environment). A total of 114 759 individuals (101 016 men [88%]; mean [SD] age, 60.1 [12.8] years) were included. In 82 707 European American individuals, a functional coding variant (rs1799971, encoding Asn40Asp) in OPRM1 (μ-opioid receptor gene, the main biological target for opioid drugs; OMIM 600018) reached genome-wide significance (G allele: β = -0.066 [SE = 0.012]; P = 1.51 × 10-8). The finding was replicated in 2 independent samples. Single-nucleotide polymorphism-based heritability of OUD was 11.3% (SE = 1.8%). Opioid use disorder was genetically correlated with 83 traits, including multiple substance use traits, psychiatric illnesses, cognitive performance, and others. Mendelian randomization analysis revealed the following associations with OUD: risk of tobacco smoking, depression, neuroticism, worry neuroticism subcluster, and cognitive performance. No genome-wide significant association was detected for African American individuals or in transpopulation meta-analysis. This genome-wide meta-analysis identified a significant association of OUD with an OPRM1 variant, which was replicated in 2 independent samples. Post-genome-wide association study analysis revealed associated pleiotropic characteristics. Recruitment of additional individuals with OUD for future studies-especially those of non-European ancestry-is a crucial next step in identifying additional significant risk loci.

Resveratrol in Cancer Patients: From Bench to Bedside.

Resveratrol (3,5,4′-trihydroxystilbene) is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review.

Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β-amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.

What do we know about actinides-proteins interactions?

Abstract Since the early 40s when the first research related to the development of the atomic bomb began for the Manhattan Project, actinides (An) and their association with the use of nuclear energy for civil applications, such as in the generation of electricity, have been a constant source of interest and fear. In 1962, the first Society of Toxicology (SOT), led by H. Hodge, was established at the University of Rochester (USA). It was commissioned as part of the Manhattan Project to assess the impact of nuclear weapons production on workers’ health. As a result of this initiative, the retention and excretion rates of radioactive heavy metals, their physiological impact in the event of acute exposure and their main biological targets were assessed. In this context, the scientific community began to focus on the role of proteins in the transportation and in vivo accumulation of An. The first studies focused on the identification of these proteins. Thereafter, the continuous development of physico-chemical characterization techniques has made it possible to go further and specify the modes of interaction with proteins from both a thermodynamic and structural point of view, as well as from the point of view of their biological activity. This article reviews the work performed in this area since the Manhattan Project. It is divided into three parts: first, the identification of the most affine proteins; second, the study of the affinity and structure of protein-An complexes; and third, the impact of actinide ligation on protein conformation and function.

Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action

Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1–4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC50 = 0.90 ± 0.08 μM) was more effective against P. falciparum than primaquine (IC50 = 1.70 ± 0.10 μM) and similar to amsacrine (IC50 = 0.80 ± 0.10 μM). In the fluorescence and UV–vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 103 M−1, indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target.

Plasma and Kidney Angiotensin Peptides: Importance of the Aminopeptidase A/Angiotensin III Axis

The renin-angiotensin system is a complex regulatory hormonal network with a main biological peptide and therapeutic target, angiotensin (Ang) II (1-8). There are other potentially important Ang peptides that have not been well evaluated. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for concurrent evaluation of multiple Angs downstream of Ang I (1-10) and Ang II (1-8) in kidney and plasma from wild-type (WT) mice. Angiotensin converting enzyme 2 knockout (ACE2KO) was also used as a way to examine the Angs profile in the absence of ACE2, an enzyme that cleaves both Ang I (1-10) and Ang II (1-8). In plasma from both WT and ACE2KO, levels of Ang I (1-10), Ang III (2-8), and Ang (2-10) were the highest of all the renin-angiotensin system (RAS) peptides. The latter two peptides are products of aminopeptidase A cleavage of Ang II (1-8) and Ang I (1-10), respectively. In contrast, plasma levels of Ang II (1-8), and Ang (1-7), the product of Ang II (1-8) cleavage by ACE2, were low. In kidney from both WT and ACE2KO, Ang II (1-8) levels were high as compared to plasma levels. In the ACE2KO mice, a significant increase in either Ang II (1-8) or a decrease in Ang (1-7) was not observed in plasma or in the kidney. RAS-focused peptidomic approach revealed major differences in Ang peptides between mouse plasma and kidney. These Ang peptide profiles show the dominance of the aminopeptidase A/Ang (2-10) and aminopeptidase A/Ang III (2-8) pathways in the metabolism of Ang I (1-10) and Ang II (1-8) over the ACE2/Ang (1-7) axis. Ang III (2-8) and other peptides formed from aminopeptidase A cleavage may be important therapeutic RAS targets.

Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity

Dual submicromolar trypanocidal–antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity.

Synthesis, DNA binding and complex formation reactions of 3-amino-5,6-dimethyl-1,2,4-triazine with Pd(II) and some selected biorelevant ligands

With the purpose of studying the binding behavior of Pd(II) complexes with DNA as the main biological target, and their ability to penetrate reasonably into tumour cells and destroy their replication ability, Pd(ADT)Cl2 complex was synthesized and characterized, where ADT is 3-amino-5,6-dimethyl-1,2,4-triazine. Stoichiometry and stability constants of the complexes formed between various biologically relevant ligands (amino acids, amides, DNA constituents, and dicarboxylic acids) and [Pd(ADT)(H2O)2]2+ were investigated at 25°C and at constant 0.1moldm−3 ionic strength. The concentration distribution diagrams of the various species formed are evaluated. Further investigation of the binding properties of the diaqua complex [Pd(ADT)(H2O)2]2+ with calf thymus DNA (CT-DNA) was investigated by UV–vis spectroscopy. The intrinsic binding constants (Kb) calculated from UV–vis absorption studies was calculated to be 2.00×103moldm−3. The calculated (Kb) value was found to be of lower magnitude than that of the classical intercalator EB (Ethidium bromide) (Kb=1.23(±0.07)×105moldm−3) suggesting an electrostatic and/or groove binding mode for the interaction with CT-DNA. Thermal denaturation has been systematically studied by spectrophotometric method and the calculated ΔTm was nearly 5°C, supporting the electrostatic and/or groove binding mode for the interaction between the complex and CT-DNA

Antimicrobial and Anti-tubercular Activity of Quinolone Analogues

Background: Quinolones are an important synthetic antimicrobial agents being used over the past three decades. Currently some quinolones are under investigation for the treatment of Mycobacterium tuberculosis and resistant strains of mycobacterium. Results: Their main biological target is the DNA gyrase, a topoisomerase-II encoded by gyrA and gyrB that is essential to maintain the DNA supercoil. The aim of this study is to collect information of the Fluoroquinolones (FQs) which are effective against tuberculosis (TB) and multidrug resistant (MDR-TB), extensively drug resistant-TB (XDR-TB) and latent TB and encourage developing of new QFs which are more effective, less toxic and shorter treatment period. Conclusion: The antitubercular (anti-TB) properties of the quinolone derivatives are as a new class of compounds with potent and selective anti-TB activities. Furthermore, particularly interesting is their activity against multidrug resistance and extensive drug resistance tuberculosis.