In silico ADMET profiling and DNA interaction study of xanthoxylin: assessment of pBR322 DNA protection against oxidative damage.

Interaction of procarbazine (PCZ) with calf thymus DNA was studied using biophysical and molecular docking studies. Procarbazine was to interact with DNA with a binding constant of 6.52×103 M-1 as calculated using ultraviolet-visible spectroscopy. To find out the binding mode, molecular docking was performed that predicted PCZ to interact with DNA through groove binding mode with binding affinity of -6.7kcal/mole. To confirm the groove binding nature, different experiments were performed. Dye displacement assays confirmed the non-intercalative binding mode. Procarbazine displaced Hoechst dye from the minor groove of DNA while it was unable to displace intercalating dyes. There was no increase in the viscosity of DNA solution in presence of PCZ. Also, negligible change in the secondary structure of DNA was observed in presence of PCZ as evident by circular dichroism spectra. Procarbazine caused decrease in the melting temperature of DNA possibly because of decrease in the stability of DNA caused by groove binding interaction of PCZ with DNA.

The interaction between antihistaminic drug oxatomide (OXT) and calf-thymus DNA (CT-DNA) has been investigated in a physiological buffer (pH 7.4) using UV–Vis, fluorescence, 1H NMR and circular dichroism spectral techniques coupled with viscosity measurements, KI quenching, voltammetry and in silico molecular modeling studies. OXT binds with CT-DNA in a concentration-dependent manner. At a lower [Drug]/[CT-DNA] molar ratio (0.6–0.1), OXT intercalates into the base pairs of CT-DNA, while at a higher [Drug]/[CT-DNA] molar ratio (13–6), the drug binds in the minor grooves of CT-DNA. The binding constants for the interaction are found to be in the order of 103–105 M−1, and the groove binding mode of interaction exhibits a slightly higher binding constant than that of intercalative mode. Thermodynamic analysis of binding constants at three different temperatures suggests that both these modes of binding are mainly driven by hydrophobic interactions (ΔH o > 0 and ΔS o > 0). Voltammetric investigations indicate that the electro-reduction of OXT is an adsorption controlled process and shifts in reduction peak potentials reiterate the concentration-dependent mode of binding of the drug with CT-DNA. The free energy landscape obtained at the all-atom level, using metadynamics simulation studies, revealed two major binding forces: partial intercalation and minor groove binding, which corroborate well with the experimental results. Communicated by Ramaswamy H. Sarma

This paper reports an interesting transformation of binding mode of 2-(4-(dimethylamino)styryl)-1-methylpyridinium iodide (DASPMI) with calf thymus DNA from minor groove binding in buffer solution to intercalative binding when the dye is encapsulated inside a vesicle formed by the interaction of 1,8-naphthalimide (a charge transfer dye) with the supramolecular association of sodium dodecyl sulfate and block-copolymer polyethylene-b-polyethylene glycol. The pre-encapsulated dye in the vesicular interior binds intercalatively to ct-DNA, as evinced by the high value of equilibrium binding constant of DASPMI-DNA complex, changes in CD-spectra of DNA and isosbestic point, along with downshift and hypochromicity of absorption band. Increase in anisotropy decay by 1.5 times with a single component strongly confirms restricted motion of the probe inside ct-DNA confirming intercalative binding. The compaction of ct-DNA caused by the interaction of the vesicle allows DASPMI to bind ct-DNA in the intercalative mode. However, the groove binding mode in ct-DNA-DASPMI remains unaffected by the retro-addition of the vesicles to the already bound dye to ct-DNA.

In this era of science, cancer is a black dot on the face of humankind. Consequently, the search of promising anticancer agents continues. Here we designed and synthesized new N-substituted rhodanines (RD1-7), evaluated their multispectroscopic interaction with calf thymus DNA, in silico and anticancer studies against MDA-MB-231cancer cell line. By MTT assay rhodanine RD1 was found to be the most potent with IC50 value of 72.61 μM. In addition, DNA binding studies (UV-vis and fluorescence) revealed strong binding affinity of RD1-7 with DNA (Kb in the range of 1.5-7.4 × 105 M-1). Moreover, molecular docking study, experimental DNA binding and anticancer studies are all well agreed to each other. It was observed that H-bonding and hydrophobic attractions were responsible for stability of DNAcompound adducts. Besides, the reported rhodanines (RD1-7) were found as minor groove binders of DNA. Concisely, RD1-7 indicated promising pharmacological properties and hence, shows auspicious future for the development of novel anticancer agents. The reported rhodanines showed excellent anticancer properties. Therefore, the described rhodanines may be used as potential anticancer agents in the future.

DNA is one of the major intracellular targets for a wide range of anticancer and antibiotic drugs. Elucidating the binding between small molecules and DNA provides great help in understanding drug-DNA interactions and in designing of new and promising drugs for clinical use. The ability of small molecules to bind and interfere with DNA replication and transcription provides further insight into how the drugs control the expression of genes. Interaction of an antimetabolite anticancer drug 6mercaptopurine (6MP) with calf thymus DNA was studied using various approaches like UV-visible spectroscopy, fluorescence spectroscopy, CD, viscosity and molecular docking. UV-visible spectroscopy confirmed 6MP-DNA interaction. Steady state fluorescence experiments revealed a moderate binding constant of 7.48×103 M−1 which was consistent with an external binding mode. Competitive displacement assays further confirmed a non-intercalative binding mode of 6MP which was further confirmed by CD and viscosity experiments. Molecular docking further revealed the minimum energy conformation (−119.67 kJ/mole) of the complex formed between DNA and 6MP. Hence, the biophysical techniques and in-silico molecular docking approaches confirmed the groove binding/electrostatic mode of interaction between 6MP and DNA. Further, photo induced generation of ROS by 6MP was studied spectrophotometrically and DNA damage was assessed by plasmid nicking and comet assay. There was a significant increase in ROS generation and consequent DNA damage in the presence of light.

Pioglitazone is an antidiabetic drug used to treat type 2 diabetes mellitus. Interaction of Pioglitazone with calf thymus DNA was investigated using multispectroscopic techniques and molecular docking study. Quenching and binding constant was calculated at 3 different temperatures. The binding constant of Pioglitazone with calf thymus DNA was calculated to be 6.49×103 M-1 at 293K. The quenching mechanism was found to be a static process, and thermodynamic parameters revealed van der Waals interactions and hydrogen bonds to be the major force working in Pioglitazone-DNA interaction. Pioglitazone follows the nonintercalative mode of binding and was involved in complex formation with DNA through minor groove binding and electrostatic interactions. Experiments like KI quenching studies, dye displacement assays, Circular Dichroism (CD) spectroscopy, DNA melting study, and viscosity measurements studies supported the nonintercalative mode of binding. This was further corroborated by molecular docking studies.

Insights into drug-DNA interactions have importance in medicinal chemistry as it has a major role in the evolution of new therapeutic drugs. Therefore, binding studies of small molecules with DNA are of significant interest. Spectroscopy, coupled with measurements of viscosity and molecular docking studies were employed to obtain mechanistic insights into the binding of altretamine with calf thymus DNA (CT-DNA). The UV-visible spectroscopic measurements study confirmed altretamine-CT-DNA complex formation with affinity constant ([15.68 ± 0.04] × 103 M−1), a value associated with groove binding phenomenon. The associated thermodynamic signatures suggest enthalpically driven interactions. The values of standard molar free energy change () -(23.93 ± 0.23) kJ mol−1, enthalpy change () -(50.84 ± 0.19) kJ mol−1 and entropy change () -(90.29 ± 0.12) JK−1 mol−1 indicate the binding is thermodynamically favorable and an important role of the hydrogen bonds and Van der Waals interactions in the binding of altretamine with CT-DNA. Circular dichroism spectroscopy indicated insignificant conformational changes in the DNA backbone upon interaction with altretamine suggesting no distortion and/or unstacking of the base pairs in the DNA helix. UV-melting study suggested that the thermal stability of the DNA backbone is not affected by the binding of the drug. Competitive displacement assays with ethidium bromide, Hoechst-33258 and DAPI established the binding of altretamine with CT-DNA in the minor groove. The mode of binding was further confirmed by viscosity and molecular docking studies. Molecular docking further ascertained binding of altretamine in the minor groove of the CT-DNA, preferably with the A-T rich sequences. Highlights Altretamine binds CT-DNA which is enthalpically driven with Ka of the order of 103 Insignificant conformational change is observed due to DNA-altretamine complexation Altretamine binds favorably with A-T rich sequences in the minor groove of CT-DNA Mechanistic insights obtained based on thermodynamic signatures Communicated by Ramaswamy H. Sarma

In the present study, a drug-like molecular hybrid structure between chalcone and sulfonamide moieties was synthesized and characterized. The structural peculiarities of the synthesized hybrid were further verified by means of single crystal X-ray crystallography. Furthermore, its biological activity as an anticancer agent was evaluated. The synthesized model of chalcone-sulfonamide hybrid 3 was found to have potent anticancer properties against the studied cancer cell lines. Hence, the in vitro binding interaction of hybrid 3 with Calf thymus DNA (CT-DNA) was studied at a simulated physiological pH to confirm its anticancer activity for the first time. This was investigated by applying different spectroscopic techniques, ionic strength measurements, viscosity measurements, thermodynamics, molecular dynamic simulation and molecular docking studies. The obtained results showed a clear binding interaction between hybrid 3 and CT-DNA with a moderate affinity via a minor groove binding mechanism. The binding constant (Kb ) at 298 K calculated from the Benesi-Hildebrand equation was found to be 3.49 × 104 M−1. The entropy and enthalpy changes (ΔS 0 and ΔH 0) were 204.65 J mol−1 K−1 and 35.08 KJ mol−1, respectively, indicating that hydrophobic interactions constituted the major binding forces. The results obtained from molecular docking and dynamic simulation studies confirmed the minor groove binding interaction and the stability of the formed complex. This study can contribute to further understanding of the molecular mechanism of hybrid 3 as a potential antitumor agent and can also guide future clinical and pharmacological studies for rational drug design with enhanced or more selective activity and greater efficacy. Communicated by Ramaswamy H. Sarma

In this study, 2(3),9(10),16(17),23(24)-tetrakis-[(N-methyl-(1-benzylpiperidin-4-yl)oxy)phthalocyaninato]zinc(II) iodide (ZnPc-2) was synthesized and characterized using spectral methods (FT-IR, 1H-NMR, UV-Vis and mass spectroscopy). The interaction of ZnPc-2 with DNA was investigated by using the UV/Vis titrimetric method, thermal denaturation profile, agarose gel electrophoresis and molecular docking studies. Additionally, the antidiabetic activity of ZnPc-2 was revealed spectroscopically by studying α-amylase and α-glucosidase inhibition activities. The spectroscopic results indicated that ZnPc-2 effectively binds to calf thymus-DNA (CT-DNA) with a Kb value of 7.5 × 104 M-1 and interacts with CT-DNA via noncovalent binding mode. Gel electrophoresis results also show that ZnPc-2 binds strongly to DNA molecules and exhibits effective nuclease activity even at low concentrations. Furthermore, docking studies suggest that ZnPc-2 exhibits a stronger binding tendency with DNA than the control compounds ethidium bromide and cisplatin. Consequently, due to its strong DNA binding and nuclease activity, ZnPc-2 may be suitable for antimicrobial and anticancer applications after further toxicological tests. Additionally, antidiabetic studies showed that ZnPc-2 had both α-amylase and α-glucosidase inhibition activity. Moreover, the α-glucosidase inhibitory effect of ZnPc-2 was approximately 3500 times higher than that of the standard inhibitor, acarbose. Considering these results, it can be said that ZnPc-2 is a moderate α-amylase and a highly effective α-glucosidase inhibitor. This suggests that ZnPc-2 may have the potential to be used as a therapeutic agent for the treatment of type 2 diabetes.

ABSTRACTIn this study, we report the synthesis and biological evaluation of novel phthalimide based Schiff base derivatives as promising antioxidant and DNA-binding agents. The structural investigation of the synthesized compounds was determined by spectral and elemental analysis. In vitro DNA-binding studies of title compounds were carried out by UV–Vis, fluorescence, circular dichroism spectroscopic techniques, cyclic voltammetry, thermal denaturation studies, and hydrodynamic measurements to investigate their potential as DNA-binding agents. The DNA binding constant (Kb) of target compounds was obtained from absorption studies between 1.2 × 105 M−1 and 1.27 × 105 M−1, respectively, suggesting that the test compounds have shown good affinity toward calf-thymus DNA. The experimental results of DNA-binding studies reveal a non-intercalative mode of binding between DNA and the synthesized compounds, most probably groove binding. In addition, molecular docking techniques were performed to rationalize the observed binding affinities with the target DNA. Furthermore, antioxidant and free radical scavenging activities of the synthesized compounds were carried out to find out their pharmacological potential. The results indicate that the title compounds displayed good antioxidant activity against DPPH (IC50: 0.727 and 0.656 mg/mL) and H2O2 radicals (IC50: 1.072 and 0.911 mg/mL) comparable to standard ascorbic acid.

Cytotoxic and genotoxic evaluation of dipyridamole and its alternative therapeutic potential in cancer therapy: an in vitro and in vivo approach.

Exploration of binding of bisphenol A and its analogues with calf thymus DNA by optical spectroscopic and molecular docking methods

Exploring the binding mechanism of Pomalidomide drug with CT-DNA: Insights from multi-spectroscopic, molecular docking and simulation studies

Dacarbazine as a minor groove binder of DNA: Spectroscopic, biophysical and molecular docking studies

Unveiling the interaction between PDT active squaraines with ctDNA: A spectroscopic study