Interaction between antidepressant drug trazodone with double-stranded DNA: Multi-spectroscopic and computational analysis.

Trazodone (TZD) is an antidepressant drug used to treat major depressive and sleeping disorders. Elevated doses of trazodone are associated with central nervous system depression, which manifests as nausea, drowsiness, confusion, vertigo, exhaustion, etc. To develop a clinically viable active pharmaceutical compound with minimal adverse effects, it is imperative to possess a comprehensive knowledge of the drug's action mechanism on DNA. Hence, we investigate the mode of interaction between trazodone and DNA utilizing various spectroscopic and computational techniques. Studies using UV-vis titration showed that the DNA and trazodone have an effective interaction. The magnitude of the Stern-Volmer constant (KSV) has been calculated to be 5.84 × 106 M-1 by the Lehrer equation from a steady-state fluorescence study. UV-vis absorption, DNA melting, dye displacement, and circular dichroism studies suggested that trazodone binds with DNA in minor grooves. Molecular docking and molecular dynamic simulation demonstrated that the TZD-DNA system was stable, and the mode of binding was minor groove. Furthermore, ionic strength investigation demonstrates that DNA and trazodone do not have a substantial electrostatic binding interaction.

Synergistic effects and competitive relationships between DOC and DOX as acting on DNA molecules: Studied with confocal Raman spectroscopy and molecular docking technology.

Docetaxel (DOC) is one of the second-generation antineoplastic drugs of the taxanes family with excellent antitumor activity. However, the mechanism of DOC inducing tumor cell apoptosis and treating cancer diseases, especially its interaction with DNA in the nucleus, and its adjuvant or combined Doxorubicin (DOX) acting on DNA molecules are unclear. In this study, the interaction mechanism between DOC and DNA, as well as the synergistic effects and competitive relationships among DOC and DOX when they simultaneously interact with DNA molecules were studied by laser confocal Raman spectroscopy combined with UV-visible absorption spectroscopy and molecular docking technology. The spectroscopic results showed that the binding constant of DOC to DNA is 5.25 × 103 M-1, the binding modes of DOC and DNA are non-classical intercalation and electrostatic binding, and the DNA-DOC complex has good stability. When DOC or DOX interacts with DNA alone, both of them can bind with bases and phosphate backbone of DNA, and also lead to DNA conformation changes; when DOC and DOX interact with DNA at the same time, the orders of interaction not only affect their binding sites with DNA, but also cause changes in the surrounding environment of the binding sites. In addition, the molecular docking results further verified that DOC and DOX have synergy and competition when they interact with DNA molecules simultaneously. The docking energies of DNA-DOC and DNA-DOX indicate the important role of van der Waals forces and hydrogen bonds. This study has practical significance for the design and development of antitumor drugs with less toxic based on the taxanes family and the combination with other drugs for the treatment of cancer.

Electrochemical Properties of Fused Pyrimidine-Triazole Heterocyclic Molecules as Novel Drug Candidates.

Objectives: Triazolopyrimidinones are compounds used in medicinal chemistry. In this study, three novel triazolopyrimidinone derivatives were synthesized as drug candidates: (5-(chloromethyl)-2-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one) (S1-TP), 2-(4-methoxyphenyl)-5-(piperidinomethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one) (S2-TP), and 2-(4-methoxyphenyl)-5-(morpholinomethyl)-[1,2,4]triazolo[1,5-a] pyrimidin-7(3H)-one) (S3-TP). Their electrochemical properties were investigated for the first time using voltammetric techniques on carbon graphite electrodes. Moreover, stability tests for each drug candidate were performed on different days. After revealing the electrochemical properties of the drug candidates, their effect on double-stranded (ds) DNA was examined by measuring the oxidation currents of the guanine of dsDNA before and after the interaction. Materials and Methods: An electrochemical setup that included a pencil graphite electrode as the working electrode, an Ag/AgCl reference electrode, and a platinum wire as the auxiliary electrode was used in this study. Experiments for optimum pH, scan rate, and concentration of drug candidates were conducted. The interaction between Ss-TP and dsDNA was evaluated using differential pulse voltammetry. The stability of each drug candidate was tested on various days. Results: A comprehensive characterization of the S1-TP, S2-TP, and S3-TP compounds was performed for the first time. This study showed that the electrochemical oxidation of S1-TP and S2-TP was irreversible and diffusion-controlled. In addition, the transfer of electrons in S3-TP was controlled by adsorption. The interaction between Ss-TP and dsDNA resulted in notable changes in the peak potentialof dsDNA. The dsDNA peak potential shifted negatively after interaction with S1-TP, S2-TP, and S3-TP. Under optimum conditions, the detection limits for S1-TP, S2-TP, and S3-TP were 1.5 µg/mL, 1.0 µg/mL, and 2.0 µg/mL, respectively. Conclusion: From our experimental data, we concluded that these molecules can be used as drug molecules because of their remarkable effects on DNA.

Electroanalysis in Pharmacogenomic Studies: Mechanisms of Drug Interaction with DNA.

The review discusses electrochemical methods for analysis of drug interactions with DNA. The electroanalysis method is based on the registration of interaction-induced changes in the electrochemical oxidation potential of heterocyclic nitrogenous bases in the DNA molecule and in the maximum oxidation current amplitude. The mechanisms of DNA-drug interactions can be identified based on the shift in the electrooxidation potential of heterocyclic nitrogenous bases toward more negative (cathodic) or positive (anodic) values. Drug intercalation into DNA shifts the electrochemical oxidation potential to positive values, indicating thermodynamically unfavorable process that hinders oxidation of nitrogenous bases in DNA. The potential shift toward the negative values indicates electrostatic interactions, e.g., drug binding in the DNA minor groove, since this process does not interfere with the electrochemical oxidation of bases. The concentration-dependent decrease in the intensity of electrochemical oxidation of DNA bases allows to quantify the type of interaction and calculate the binding constants.

Pharmacogenomic Studies of Antiviral Drug Favipiravir.

In this work, we conducted a study of the interaction between DNA and favipiravir (FAV). This chemotherapeutic compound is an antiviral drug for the treatment of COVID-19 and other infections caused by RNA viruses. This paper examines the electroanalytical characteristics of FAV. The determined concentrations correspond to therapeutically significant ones in the range of 50-500 µM (R2 = 0.943). We have shown that FAV can be electro-oxidized around the potential of +0.96 V ÷ +0.98 V (vs. Ag/AgCl). A mechanism for electrochemical oxidation of FAV was proposed. The effect of the drug on DNA was recorded as changes in the intensity of electrochemical oxidation of heterocyclic nucleobases (guanine, adenine and thymine) using screen-printed graphite electrodes modified with single-walled carbon nanotubes and titanium oxide nanoparticles. In this work, the binding constants (Kb) of FAV/dsDNA complexes for guanine, adenine and thymine were calculated. The values of the DNA-mediated electrochemical decline coefficient were calculated as the ratio of the intensity of signals for the electrochemical oxidation of guanine, adenine and thymine in the presence of FAV to the intensity of signals for the electro-oxidation of these bases without drug (S, %). Based on the analysis of electrochemical parameters, values of binding constants and spectral data, intercalation was proposed as the principal mechanism of the antiviral drug FAV interaction with DNA. The interaction with calf thymus DNA also confirmed the intercalation mechanism. However, an additional mode of interaction, such as a damage effect together with electrostatic interactions, was revealed in a prolonged exposure of DNA to FAV.

Synthesis, structure elucidation, SC-XRD/DFT, molecular modelling simulations and DNA binding studies of 3,5-diphenyl-4,5-dihydro-1H-pyrazole chalcones.

Deoxyribonucleic acid (DNA) acts as the most important intracellular target for various drugs. Exploring the DNA binding interactions of small bioactive molecules offers a structural guideline for designing new drugs with higher clinical efficacy and enhanced selectivity. This study presents the facile synthesis of pyrazoline-derived compounds (4a)-(4f) by reacting substituted chalcones with hydrazine hydrate using formic acid. The structure elucidation of substituted pyrazoline compounds was carried out using 1H-NMR, FT-IR and elemental analyses. While the crystal structures of two compounds (4a) and (4b) have been resolved by single-crystal X-ray diffraction (SC-XRD) analysis. Hirshfeld surface analysis also endorsed their greater molecular stability. Computational calculations at DFT/B3LYP/6-311++G(d,p) were executed to compare the structural properties (bond angle and bond length) and explore reactivity descriptors, frontier molecular orbitals (FMO), Mulliken atomic charges (MAC), molecular electrostatic potential (MEP) and electronic properties. All the compounds were evaluated for DNA binding interactions by UV-Vis spectrophotometric analysis. The results revealed that compounds (4a)-(4f) bind to DNA via non-covalent binding mode having binding constant values ranging from 1.22 × 103 to 6.81 × 104 M-1. The negative values of Gibbs free energy also proved the interaction of studied compounds with DNA as a spontaneous process. The findings of molecular docking simulations depicted that these studied compounds showed significant binding interactions with DNA and these results were consistent with experimental findings. Compound (4b) was concluded as the most potent compound of the series with the highest binding constant (4.95 × 104) and strongest binding affinity (-8.48 kcal/mol).Communicated by Ramaswamy H. Sarma.

Studying the Interaction between Bendamustine and DNA Molecule with SERS Based on AuNPs/ZnCl2/NpAA Solid-State Substrate.

Bendamustine (BENDA) is a bifunctional alkylating agent with alkylating and purinergic antitumor activity, which exerts its anticancer effects by direct binding to DNA, but the detailed mechanism of BENDA-DNA interaction is poorly understood. In this paper, the interaction properties of the anticancer drug BENDA with calf thymus DNA (ctDNA) were systematically investigated based on surface-enhanced Raman spectroscopy (SERS) technique mainly using a novel homemade AuNPs/ZnCl2/NpAA (NpAA: nano porous anodic alumina) solid-state substrate and combined with ultraviolet-visible spectroscopy and molecular docking simulation to reveal the mechanism of their interactions. We experimentally compared and studied the SERS spectra of ctDNA, BENDA, and BENDA-ctDNA complexes with different molar concentrations (1:1, 2:1, 3:1), and summarized their important characteristic peak positions, their peak position differences, and hyperchromic/hypochromic effects. The results showed that the binding modes include covalent binding and hydrogen bonding, and the binding site of BENDA to DNA molecules is mainly the N7 atom of G base. The results of this study help to understand and elucidate the mechanism of BENDA at the single-molecule level, and provide guidance for the further development of effective new drugs with low toxicity and side effects.

Interaction of Doxorubicin Embedded into Phospholipid Nanoparticles and Targeted Peptide-Modified Phospholipid Nanoparticles with DNA.

The interactions of dsDNA with new targeted drug delivery derivatives of doxorubicin (DOX), such as DOX embedded into phospholipid nanoparticles (NPhs) and DOX with the NGR targeted peptide-modified NPhs were studied electrochemically by differential pulse voltammetry technique. Screen-printed electrodes (SPEs), modified with stable fine dispersions of carbon nanotubes (CNTs), were used for quantitative electrochemical investigations of direct electrochemical oxidation of guanine, adenine, and thymine heterocyclic bases of dsDNA, and their changes in the presence of DOX nanoderivatives. Analysing the shifts of peak potentials of nucleobases in the presence of drug, we have shown that the doxorubicin with NGR targeted peptide changed the mode of interaction in DNA-drug complexes from intercalative to electrostatic. Binding constants (Kb) of DNA-drug complexes were calculated in accordance with adenine, guanine, and thymine oxidation signals. Based on our experiments, we have proven that the surface modification of a drug delivery system with NGR targeted peptide dramatically changed the mechanism of interaction of drug with genetic material. DNA-mediated drug toxicity was calculated based on the concentration-dependent "response" of heterocyclic nucleobases on drug influence. DOX, DOX-loaded phospholipid nanoparticles (NPhs), and DOX with NGR addressed peptide-modified NPhs were moderately toxic in the concentration range of 0.5-290 µM.

A novel electrochemical biosensor based on palladium nanoparticles decorated on reduced graphene oxide-polyaminophenol matrix for the detection and discrimination of mitomycin C-DNA and acyclovir-DNA interaction.

Both the design of molecules that will interact specifically with DNA and the determination of the mechanism of action of this drug on DNA are important as they allow the control of gene expression. In particular, rapid and precise analysis of this type of interaction is a vital element for pharmaceutical studies. In the present study, a novel reduced graphene oxide/ palladium nanoparticles/ poly(2-amino-4-chlorophenol) (rGO/Pd@PACP) nanocomposite was synthesized by chemical process to modify pencil graphite electrode (PGE) surface. Here, the performance of the newly developed nanomaterial-based biosensor for drug-DNA interaction analysis has been demonstrated. For this purpose, it was determined whether this system, which was developed by selecting a drug molecule (Mitomycin C; MC) known to interact with DNA and a drug molecule (Acyclovir; ACY) that does not interact with DNA, performs a reliable/accurate analysis. Here, ACY was used as a negative control. Compared to bare PGE, the rGO/Pd@PACP nanomaterial modified sensor exhibited 17 times higher sensitivity performance in terms of guanine oxidation signal measured by differential pulse voltammetry (DPV). Moreover, the developed nanobiosensor system provided a highly specific determination between the anticancer drug MC and ACY by discrimination the interactions of these drugs with double-stranded DNA (dsDNA). ACY was also preferred in studies for the optimization of the new nanobiosensor developed. ACY was detected in a concentration as low as 0.0513 µM (51.3 nM) (LOD), and limit of quantification (LOQ) was 0.1711 µM with a linear range from 0.1 to 0.5 µM.

Elucidating the interaction of antidepressant drug paroxetine with ct-dsDNA: A comparative study by electrochemical, spectroscopic, and molecular docking approaches.

This study is designed to investigate the interaction of phenylpiperidine derivative drug paroxetine, which is an effective serotonin reuptake inhibitor and biomolecules through electrochemical, fluorescence spectroscopy, and molecular docking methods. The interaction between paroxetine and biomolecules was investigated by differential pulse voltammetry according to the decrease in deoxyguanosine anodic oxidation signal of double-stranded calf thymus DNA. Fluorescence spectroscopy studies were performed by titrating paroxetine against double-stranded calf thymus DNA solution at four different temperatures. The fluorescent results showed that paroxetine had a great affinity to bind with double-stranded calf thymus DNA. Interaction studies demonstrate that paroxetine binds to double-stranded calf thymus DNA via intercalation binding mode, and the binding constant values ​​were calculated as 7.24 × 104 M-1 and 1.52 × 104 M-1 at 25 °C, based on voltammetric and spectroscopic results, respectively. Moreover, with the aim of elucidating the interaction mechanism between paroxetine and double-stranded calf thymus DNA, electrochemical and fluorescence spectroscopy studies along with molecular docking analysis were made.

Achievements of Graphene and Its Derivatives Materials on Electrochemical Drug Assays and Drug-DNA Interactions.

Graphene, emerging as a true two-dimensional (2D) material, has attracted increasing attention due to its unique physical and electrochemical properties such as high surface area, excellent conductivity, high mechanical strength, and ease of functionalization and mass production. The entire scientific community recognizes the significance and potential impact of graphene. Electrochemical detection strategies have advantages such as being simple, fast, and low-cost. The use of graphene as an excellent interface for electrode modification provides a promising way to construct more sensitive and stable electrochemical (bio)sensors. The review presents sensors based on graphene and its derivatives for electrochemical drug assays from pharmaceutical dosage forms and biological samples. Future perspectives in this rapidly developing field are also discussed. In addition, the interaction of several important anticancer drug molecules with deoxyribonucleic acid (DNA) that was immobilized onto graphene-modified electrodes has been detailed in terms of dosage regulation and utility purposes.

Electrochemical DNA biosensors developed for the monitoring of biointeractions with drugs: a review.

The interaction of drugs with DNA is important for the discovery of novel drug molecules and for understanding the therapeutic effects of drugs as well as the monitoring of side effects. For this reason, many studies have been carried out to investigate the interactions of drugs with nucleic acids. In recent years, a large number of studies have been performed to electrochemically detect drug-DNA interactions. The fast, sensitive, and accurate results of electrochemical techniques have resulted in a leading role for their implementation in this field. By means of electrochemical techniques, it is possible not only to demonstrate drug-DNA interactions but also to quantitatively analyze drugs. In this context, electrochemical biosensors for drug-DNA interactions have been examined under different headings including anticancer, antiviral, antibiotic, and central nervous system drugs as well as DNA-targeted drugs. An overview of the studies related to electrochemical DNA biosensors developed for the detection of drug-DNA interactions that were reported in the last two decades in the literature is presented herein along with their applications and they are discussed together with their future perspectives.

Simultaneous determination of aesculin and aesculetin and their interactions with DNA using carbon fiber microelectrode modified by Pt-Au bimetallic nanoparticles.

Electrode sensitivity and selectivity in complex biological matrices are major challenges in the development of electrochemical sensors. Bimetallic nanoparticles provide a new perspective for enhancing electrocatalytic property because of some specific synergetic effects. In this work, platinum nanoparticles (PtNPs) and gold nanoparticles (AuNPs) modified carbon fiber microelectrode (PtNPs/AuNPs/CFME) was fabricated to determine aesculin and aesculetin simultaneously. Differential pulse voltammetry (DPV) method was conducted for the electrochemical sensing of aesculin and aesculetin, the modified electrode displayed high electrocatalytic activity for the redox of these two drugs. The linear ranges of aesculin and aesculetin were 0.4-10 µM and 0.04-1 µM, with the detection limits of 41 nM and 3.6 nM, respectively, which were the lowest values achieved. Furthermore, an electrochemical investigation of the interactions of these two drugs with Calf thymus double stranded DNA (dsDNA) was investigated by PtNPs/AuNPs/CFME, the decrease in peak currents is proportional to DNA concentration and can be used to detect DNA. The electrode was successfully used to measure aesculin and aesculetin in mouse serum and urine with 98.0-104.8% recovery. The novel electrochemical probe possessed excellent performances of high sensitivity, good reproducibility, and simplicity of fabrication, which will facilitate effective detection of aesculin and aesculetin for metabolic kinetics study.

The Interaction between DNA and Three Intercalating Anthracyclines Using Electrochemical DNA Nanobiosensor Based on Metal Nanoparticles Modified Screen-Printed Electrode.

The screen-printed electrodes have gained increasing importance due to their advantages, such as robustness, portability, and easy handling. The manuscript presents the investigation of the interaction between double-strand deoxyribonucleic acid (dsDNA) and three anthracyclines: epirubicin (EPI), idarubicin (IDA), and doxorubicin (DOX) by differential pulse voltammetry on metal nanoparticles modified by screen-printed electrodes. In order to investigate the interaction, the voltammetric signals of dsDNA electroactive bases were used as an indicator. The effect of various metal nanomaterials on the signals of guanine and adenine was evaluated. Moreover, dsDNA/PtNPs/AgNPs/SPE (platinum nanoparticles/silver nanoparticles/screen-printed electrodes) was designed for anthracyclines-dsDNA interaction studies since the layer-by-layer modification strategy of metal nanoparticles increases the surface area. Using the signal of multi-layer calf thymus (ct)-dsDNA, the within-day reproducibility results (RSD%) for guanine and adenine peak currents were found as 0.58% and 0.73%, respectively, and the between-day reproducibility results (RSD%) for guanine and adenine peak currents were found as 1.04% and 1.26%, respectively. The effect of binding time and concentration of three anthracyclines on voltammetric signals of dsDNA bases were also evaluated. The response was examined in the range of 0.3-1.3 ppm EPI, 0.1-1.0 ppm IDA and DOX concentration on dsDNA/PtNPs/AgNPs/SPE. Electrochemical studies proposed that the interaction mechanism between three anthracyclines and dsDNA was an intercalation mode.

Electrochemical determination of anticancer drug Bendamustine and its interaction with double strand DNA in the absence and presence of quercetin.

Studies based on drug-DNA interactions, especially anticancer drug-DNA interactions, are of great importance for the method development. It is thought that single-use electrodes, which give fast, cheap and reproducible results, will make a great contribution to the chip technology for the development of individual patient analysis in the future. It is known that antioxidants reduce carcinogenesis caused by oxidative stress with their radical scavenging effects. Literature shows that quercetin (QRCT) exhibits anticancer activity by preventing oxidative cell damage as an effective radical scavenger. In this study, Bendamustine (BND), an anticancer drug, which is used in different blood cancer types, was electrochemically determined and the toxicity degree was calculated by examining the interaction of the drug with DNA in the absence and presence of QRCT, which is the first examination in the literature. Limit of detection and quantification for BND was calculated as 6.0 and 20.0 µg/mL respectively by using the equation I = 0.029 × CBND+ 1.197, (R2 = 0.997). We found that QRCT prevents the interaction between BND and DNA because of its strong interaction with DNA.

Hybrid nanoflowers modified pencil graphite electrodes developed for electrochemical monitoring of interaction between Mitomycin C and DNA.

In the present study, biocompatible hybrid nanoflowers (NFs) were synthesized by amino acids (glycine, l-lysine) via a simple, rapid and cost-effective methods. NFs were characterized by using FT-IR, Raman spectroscopy, XPS, SEM and EDX techniques. Modified pencil graphite electrode (PGE) surfaces with well-defined NFs were developed to electrochemical monitoring of calf thymus double stranded DNA (ctdsDNA) using differential pulse voltammetry (DPV) for the first time. SEM, EDX, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used to characterize the surfaces obtained after modification. In comparison to l-lysine NFs (LNFs-PGE), glycine NFs (GNFs-PGE) exhibited a higher sensitivity performance towards the oxidation of guanine moiety signals. The interaction time between anticancer drug Mitomycin C (MC) and ctdsDNA was aslo investigated with GNFs-PGE.

Four-way parallel factor analysis of voltammetric four-way dataset for monitoring the etoposide-DNA interaction with its binding constant determination.

In this paper, a novel strategy in the application of the parallel factor analysis (PARAFAC) to a four-way voltammetric dataset was improved to evidence the interaction of etoposide (ETO) and calf thymus deoxyribonucleic acid (DNA) to determine the ETO-DNA binding constant. PARAFAC is one of the most commonly used techniques applicable to the decomposition of higher-order data arrays to focus on features of interest and provides a different resolution of the chemical problem of interest. Under optimized conditions, peak current data of a seven-sample set containing DNA in the range of 2.0-90.0 µM in the presence of ETO at a constant concentration (10 µM) at five different pHs were recorded as a function of potential and frequency and then arranged as a four-dimensional array. The characteristic curves of ETO and ETO-DNA complex were monitored from the potential, frequency, pH, and DNA concentration profiles obtained by PARAFAC decomposition of the fourth-order array. The binding constant, which is one of the principal parameters for the estimation of drug-DNA interaction and mechanism, was computed from the DNA concentration profile. The consequence of drug-DNA binding constant (K = 1.26 × 106) indicated that there was a significant interaction between ETO and DNA with the intercalation mechanism.

Revealing the Energetics of Ligand-Quadruplex Interactions Using Isothermal Titration Calorimetry.

The thermodynamic characterization of G4-ligand interactions has shown to be a powerful adjunct to structural information in the rational design and optimization of potent G-quadruplex ligands for use in therapeutics, diagnostics, or other technological applications. Isothermal titration calorimetry (ITC) can resolve energetic contributions to complex formation and constitutes the only available experimental method to directly measure binding enthalpies. A general protocol for using ITC in studies on quadruplex-ligand interactions with details on the experimental setup, data analysis, and potential pitfalls is presented. The methodologies used are illustrated on results obtained from the targeting of a parallel DNA G-quadruplex with a G4-binding indoloquinoline derivative.

DNA minor groove binding of a well known anti-mycobacterial drug dapsone: A spectroscopic, viscometric and molecular docking study.

Dapsone is a sulfone drug mainly used as anti-microbial and anti-inflammatory agent for the treatment of various diseases including leprosy. Recently, its interaction with protein (bovine serum albumin) is evidenced. But, the binding propensity of this anti-mycobacterial drug towards DNA is still unknown. Also, the mode of dapsone-DNA interaction (if any) is still an unknown quantity. In this study, we have taken a thorough attempt to understand these two unknown aspects using various biophysical and in silico molecular docking techniques. Both UV-visible and fluorescence titrimetric studies indicated that dapsone binds to CT-DNA with a binding constant in order of 104 M-1. Circular dichroism, thermal denaturation and viscosity experiments revealed that dapsone binds to the grooves of CT-DNA. Competitive DNA binding studies clearly indicated the minor groove binding property of this anti-mycobacterial drug. Molecular docking provided detailed information about the formation of hydrogen bonding in the dapsone-DNA complex. This in silico study further revealed that dapsone binds to the AT-rich region of the minor groove of DNA having a relative binding energy of -6.22 kcal mol-1. Overall, all these findings evolved from this study can be used for better understanding the medicinal importance of dapsone.

Depicting the DNA binding and photo-nuclease ability of anti-mycobacterial drug rifampicin: A biophysical and molecular docking perspective.

Rifampicin, an important member of ansamycin family, exhibits various biological activities. It is frequently used for the treatment of tuberculosis and leprosy. Recently, its interaction with protein is evidenced. But, its interaction with DNA is still unknown. Whether, exhibition of anti-cancer activity of rifampicin is associated with DNA-cleavage activity is also unknown. In this study, an attempt has been taken to understand these two unknown aspects. Spectroscopic studies indicated that rifampicin binds to CT-DNA with a binding constant of ~5.22 × 105 M-1. Several independent experiments like CD analysis, competitive displacement experiments and viscosity measurements revealed that rifampicin intercalates into the CT-DNA. Molecular docking studies corroborate this fact and depicted that this drug binds to the GC-rich region of DNA through multiple hydrogen bonding having the relative binding energy of -9.21 kcal mol-1. Besides, DNA binding ability, rifampicin causes the photo-cleavage of pUC19 DNA via singlet oxygen pathway. To the best of our knowledge, we report for the first time the DNA binding and DNA cleavage ability of rifampicin. This study provides a clue behind the execution of the anti-cancer activity of rifampicin. Overall, all these information can be used for further understanding the pharmacological effects of rifampicin.