Kappa-carrageenan and sodium alginate-based pH-responsive hydrogels for controlled release of methotrexate.

Despite remarkable progress in medical sciences, modern man is still fighting the battle against cancer. In 2022, only in the USA, 640 000 deaths and 2 370 000 patients were reported because of cancer. Chemotherapy is the most widely used for cancer treatments. However, chemotherapeutics have severe physicochemical side effects. Therefore, we have prepared poly(amididoamine) dendrimeric carrageenan (CG), sodium alginate (SA) and poly(vinyl alcohol) (PVA) hydrogels by using solution casting methodology. The constituents of hydrogels were cross-linked by mutable quantity of 3-aminopropyl(diethoxy)methyl silane (APDMS). Hydrogels were characterized by Fourier transform infrared spectroscopy, thermal gravimetric analysis, scanning electron microscope and atomic force microscopy. Hydrogels exhibited higher swelling volumes in 5-7 pH range. In vitro biodegradation in ribonuclease-A solution and cytocompatibility analysis against DF-1 fibroblasts established their biodegradable and non-toxic nature, which enables them as a suitable carrier for chemotherapeutic compounds. Hence, methotrexate (MTX) as a model drug was loaded on CAP-8 hydrogel and its release was detected by the UV-visible spectrophotometer in phosphate-buffered saline (PBS) solution. In 13.5 h, 81.25% and 77.23% of MTX were released at pH 7.4 (blood pH) and 5.3 (tumour pH) in PBS, respectively. MTX was released by super case II mechanism and best fitted to zero-order and Korsmeyer-Peppas model. The synthesized APDMS cross-linked CG/SA/PVA dendrimeric hydrogels could be an efficient model platform for the effective delivery of MTX in cancer treatments.

Efficient removal of toxic azo dyes from contaminated water by adsorption on the GO surface.

The purpose of this study is to examine the possibility of GO to be used as an adsorbent for five novel potentially hazardous azo-dyes for their removal from aqueous solution. Adsorption characteristics of GO for azo-dyes removal were investigated by means of experimental and computational DFT as well as Monte Carlo approaches. Experimental studies include the effect of adsorbent dose, contact time, and initial concentration, while computational investigation involves DFT and Monte Carlo (MC) simulations. Through DFT studies geometric, electronic, and thermodynamic parameters were explored and possible mechanism of interactions and adsorption energies by predicted through MC by searching lowest possible adsorption complexes. Experimental data were evaluated by Langmuir models in order to describe the equilibrium isotherms. Equilibrium data fitted well to the Langmuir model. Thermodynamic parameters i.e., free energy change, enthalpy change, and entropy change revealed that the removal of azo-dyes by adsorption on the surface of GO molecular sieves was spontaneous. Nature of the process was found to be physiosorption involving non-covalent interaction. The study unveiled that GO can be used as an efficient adsorbent material for the adsorption of azo-dyes from aqueous solution.

Exploration of newly synthesized amantadine-thiourea conjugates for their DNA binding, anti-elastase, and anti-glioma potentials.

Three newly synthesized amantadine thiourea conjugates namely MS-1 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)benzamide, MS-2 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)-4-methylbenzamide and MS-3 N-((3 s,5 s,7 s)-adamantan-1-ylcarbamothioyl)-4-chlorobenzamide were investigated for their structures, bindings (DNA/ elastase), and for their impact on healthy and cancerous cells. Theoretical (DFT/docking) and experimental {UV-visible (UV-), fluorescence (Flu-), and cyclic voltammetry (CV)} studies indicated binding interactions of each conjugate with DNA and elastase enzyme. Theoretically and experimentally calculated binding parameters for conjugate - DNA interaction revealed MS-3 - DNA to have most significant binding with comparatively greater values of binding parameters {(Kb/M-1: docking, 3.8 × 105; UV-, 5.95 × 103; Flu-,1.55 × 105; CV, 1.52 × 104), (∆G/ kJmol-1: docking, -32.09; UV-, -22.40; Flu-,-30.81; CV, -24.82)}. The docked structures, greater bindings site size values (n), and the trend in DNA viscosity changes in the presence of each conjugate concentration confirmed a mixed binding mode of interaction among them. Conjugate - elastase binding by docking agreed with the experimental anti-elastase findings. Cytotoxicity studies of each tested conjugate demonstrated greater cytotoxicity for cancerous (MG-U87) cells in comparison to control, while for the normal (HEK-293) cells the cytotoxicity was found comparatively low. Overall exploration suggested that MS-3 is the most effective candidate for DNA binding, anti-elastase, and for anti-glioma activities.

Exploration of anode candidacy of Ni0.2Co2.8O4 and integrated Ni0.2Co2.8O4/MWCNTs in supercapacitor and oxygen evolution reaction.

In the current research work, Ni0.2Co2.8O4 and Ni0.2Co2.8/MWCNTs have been synthesized via facile sol-gel and wet impregnation method. The synthesized materials attained the crystalline structures as evident from X-ray diffraction analysis (XRD). The uniform morphology and well dispersion of Ni0.2Co2.8O4 onto MWCNTs was observed via scanning electron microscopy (SEM). The electrochemical investigations for supercapacitor application by cyclic voltammetry (CV), galvanostatic charge discharge (GCD), and electrochemical impedance spectroscopy (EIS) revealed that, among both materials, Ni0.2Co2.8O4/MWCNTs has high specific capacitance (CV; 505.8 Fg-1 at 5 mV/s, GCD; 1598 Fg-1 at 0.5 A/g), greater capacitance retention (85 %) at 1000 cycles and has lower charge transfer resistance (Rct; 3.48 Ω cm2). These findings reflected the potential candidacy of Ni0.2Co2.8O4/MWCNTs to be used as anode material in supercapacitor. Further investigations by CV and linear sweep voltammetry (LSV) for oxygen evolution reaction (OER) activity in 1.0 M KOH showed comparatively low over potential of 340 mV @100 mA/cm2 for the same integrated material. Additionally, the lower Tafel slope (47 mV/dec) and solution resistance authenticated it as an appropriate electrocatalyst for OER in water splitting. The CPE (controlled potential electrolysis) revealed the stability of both materials for OER in water oxidation.

Guar gum-based stimuli responsive hydrogels for sustained release of diclofenac sodium.

In the current study, hydrogels for the controlled release of diclofenac sodium were synthesized from graphene oxide-reinforced guar gum and poly (N-vinyl-2-pyrrolidone) using the Solution Casting Technique. Varying concentrations of 3-Glycidyloxypropyl trimethoxysilane (GLYMO) were employed for the crosslinking of hydrogels. Further, the characterization of hydrogels was carried out using different techniques such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction, thermal analysis and scanning electron microscope. The FTIR investigations reveals particular functionalities and development of hydrogel interfaces. While thermal analysis prophesied that, improvement in forces among hydrogel components is directly proportional to the GLYMO concentration. In-vitro biodegradation test and cell viability assay against HEK-293 cell lines confirmed their biodegradable and biocompatible nature. GPG-32 demonstrated maximum antibacterial activity against P.aeruginosa and E.coli strains. The maximum swelling 2001 % and 1814 % in distilled water were recorded for GPG (control) and GPG-8 respectively that obeyed Fick's law. Hydrogels displayed high swelling responses at pH 6 in buffer and non-buffer solutions. In 2.5 h, 88.7 % diclofenac sodium was released which was determined by UV visible spectrophotometer. In conclusion, guar gum-based non-toxic, biocompatible and biodegradable hydrogels would be a model platform for targeting inflammation and pains. Furthermore, improved mechanical and viscoelastic behavior of hydrogels could also be explored for making drug loaded dressings for wound healing applications.

Graphene oxide reinforced biopolymeric (chitosan) hydrogels for controlled cephradine release.

In the current study, chitosan, poly (N-vinyl-2-pyrolidone) and polyamidoamine based hydrogels were prepared by Solution Casting Method using different quantity of graphene oxide (GO) for controlled cephradine (CPD) release. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis, scanning electron microscope and atomic force microscopy. FTIR results endorsed the presence of particular functionalities and developed interfaces in hydrogels. The thermal stability was directly proportional to the amount of GO. Antibacterial activity was investigated against gram-negative bacteria resultantly; CAD-2 exhibited maximum bactericidal activity against Escherichia coli and Psuedomonas aeruginosa. In addition, in-vitro biodegradation was examined in phosphate buffer saline solution and proteinase K for 21 and 07 days respectively. The maximum swelling was exhibited by CAD-133777 % in distilled water that was governed by quasi-Fickian diffusion. The swelling volumes were inversely proportional to the amount of GO. In the same way, pH sensitive CPD release was detected by UV visible spectrophotometer that followed zero order and Higuchi models. However, in 4 h, 89.4 % and 83.7 % of CPD was released in PBS and SIF solution correspondingly. Therefore, the chitosan-based biocompatible and biodegradable hydrogel platforms offered substantial potential for the controlled CPD release in medico-biological applications.

Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities.

Bis-acyl-thiourea derivatives, namely N,N'-(((4-nitro-1,2-phenylene)bis(azanediyl)) bis(carbonothioyl))bis(2,4-dichlorobenzamide) (UP-1), N,N'-(((4-nitro-1,2-phenylene) bis(azanediyl))bis(carbonothioyl))diheptanamide (UP-2), and N,N'-(((4-nitro-1,2-phenylene)bis(azanediyl))bis(carbonothioyl))dibutannamide (UP-3), were synthesized in two steps. The structural characterization of the derivatives was carried out by FTIR, 1H-NMR, and 13C-NMR, and then their DNA binding, anti-urease, and anticancer activities were explored. Both theoretical and experimental results, as obtained by density functional theory, molecular docking, UV-visible spectroscopy, fluorescence (Flu-)spectroscopy, cyclic voltammetry (CV), and viscometry, pointed towards compounds' interactions with DNA. However, the values of binding constant (Kb), binding site size (n), and negative Gibbs free energy change (ΔG) (as evaluated by docking, UV-vis, Flu-, and CV) indicated that all the derivatives exhibited binding interactions with the DNA in the order UP-3 > UP-2 > UP-1. The experimental findings from spectral and electrochemical analysis complemented each other and supported the theoretical analysis. The lower diffusion coefficient (Do) values, as obtained from CV responses of each compound after DNA addition at various scan rates, further confirmed the formation of a bulky compound-DNA complex that caused slow diffusion. The mixed binding mode of interaction as seen in docking was further verified by changes in DNA viscosity with varying compound concentrations. All compounds showed strong anti-urease activity, whereas UP-1 was found to have comparatively better inhibitory efficiency, with an IC50 value of 1.55 ± 0.0288 µM. The dose-dependent cytotoxicity of the synthesized derivatives against glioblastoma MG-U87 cells (a human brain cancer cell line) followed by HEK-293 cells (a normal human embryonic kidney cell line) indicated that UP-1 and UP-3 have greater cytotoxicity against both cancerous and healthy cell lines at 400 µM. However, dose-dependent responses of UP-2 showed cytotoxicity against cancerous cells, while it showed no cytotoxicity on the healthy cell line at a low concentration range of 40-120 µM.

Structure and surface analyses of a newly synthesized acyl thiourea derivative along with its in silico and in vitro investigations for RNR, DNA binding, urease inhibition and radical scavenging activities.

N-((4-Acetylphenyl)carbamothioyl)-2,4-dichlorobenzamide (4) was synthesized by the treatment of 2,4-dichlorobenzoyl chloride with potassium thiocyanate in a 1 : 1 molar ratio in dry acetone to afford the 2,4-dichlorobenzoyl isothiocyanate in situ which on reaction with acetyl aniline furnished (4) in good yield and high purity. The compound was confirmed by FTIR, 1H-NMR, and 13C-NMR and single crystal X-ray diffraction studies. The planar rings were situated at a dihedral angle of 33.32(6)°. The molecules, forming S(6) ring motifs with the intramolecular N-H⋯O hydrogen bonds, were linked through intermolecular C-H⋯O and N-H⋯S hydrogen bonds, enclosing R2 2(8) ring motifs, into infinite double chains along [101]. C-H⋯π and π⋯π interactions with an inter-centroid distance of 3.694 (1) Å helped to consolidate a three-dimensional architecture. Hirshfeld surface (HS) analysis further indicated that the most important contributions for the crystal packing were from H⋯C/C⋯H (20.9%), H⋯H (20.5%), H⋯Cl/Cl⋯H (19.4%), H⋯O/O⋯H (13.8%) and H⋯S/S⋯H (8.9%) interactions. Thus C-H⋯π (ring), π⋯π, van der Waals interactions and hydrogen bonding played the major roles in the crystal packing. The electronic structure and computed DFT (density functional theory) parameters identified the reactivity profile of compound (4). In silico binding of (4) with RNA indicated the formation of a stable protein-ligand complex via hydrogen bonding, while DNA docking studies inferred (4) as a potent groove binder. The experimentally observed hypochromic change (57.2%) in the UV-visible spectrum of (4) in the presence of varying DNA concentrations together with the evaluated binding parameters (K b; 7.9 × 104 M-1, ΔG; -28.42 kJ mol-1) indicated spontaneous interaction of (4) with DNA via groove binding and hence supported the findings obtained through docking analysis. This compound also showed excellent urease inhibition activity in both in silico and vitro studies with an IC50 value of 0.0389 ± 0.0017 µM. However, the radical scavenging efficiency of (4) was found to be modest in comparison to vitamin C.

Investigations on the Morphological, Mechanical, Ablative, Physical, Thermal, and Electrical Properties of EPDM-Based Composites for the Exploration of Enhanced Thermal Insulation Potential.

The most widely used filler in EPDM-based thermal insulation materials is asbestos which is hazardous to health and environment. The main motivation of this study was to develop improved EPDM-based materials by partially or completely replacing asbestos with other fillers. EPDM-Esprene501A and EPDM-Keltan®4869DE were used and the effect of three fillers (vulkasil-C, asbestos, carbon fiber fabric) on mechanical, ablative, physical, thermal, and electrical performances have been investigated. Samples were divided into phase -1, -2, and -3 by compounding EPDM with various percentages of fillers and other necessary ingredients. It was observed that asbestos and carbon fiber in the absence of vulkasil-C did not import enough reinforcement to EPDM-matrix. Experimental evidence showed that presence of vulkasil-C has not only enhanced mechanical properties but also improved thermal and ablation performance of EPDM-based composites. The swelling index was found comparatively lower with vulkasil-C than that with other fillers. Among two EPDMs, EPDM-Esprene based composites have shown comparatively better performance. Among all (phase-1-3) samples, E100K0VA (phase-2) has shown greater mechanical (stress 3.89 MPa; strain 774%), ablative (linear 0.1 mm/s; mass 0.05 g/s), and thermal (material left 91.0%) properties. Overall findings indicated improved properties of EPDM in the presence of vulkasil-C and may help to develop better heat resistant materials.

Investigations on Anticancer Potentials by DNA Binding and Cytotoxicity Studies for Newly Synthesized and Characterized Imidazolidine and Thiazolidine-Based Isatin Derivatives.

Imidazolidine and thiazolidine-based isatin derivatives (IST-01-04) were synthesized, characterized, and tested for their interactions with ds-DNA. Theoretical and experimental findings showed good compatibility and indicated compound-DNA binding by mixed mode of interactions. The evaluated binding parameters, i.e., binding constant (Kb), free energy change (ΔG), and binding site sizes (n), inferred comparatively greater and more spontaneous binding interactions of IST-02 and then IST-04 with the DNA, among all compounds tested under physiological pH and temperature (7.4, 37 °C). The cytotoxic activity of all compounds was assessed against HeLa (cervical carcinoma), MCF-7 (breast carcinoma), and HuH-7 (liver carcinoma), as well as normal HEK-293 (human embryonic kidney) cell lines. Among all compounds, IST-02 and 04 were found to be cytotoxic against HuH-7 cell lines with percentage cell toxicity of 75% and 66%, respectively, at 500 ng/µL dosage. Moreover, HEK-293 cells exhibit tolerance to the increasing drug concentration, suggesting these two compounds are less cytotoxic against normal cell lines compared to cancer cell lines. Hence, both DNA binding and cytotoxicity studies proved imidazolidine (IST-02) and thiazolidine (IST-04)-based isatin derivatives as potent anticancer drug candidates among which imidazolidine (IST-02) is comparatively the more promising.

Synthesis, X-ray, Hirshfeld surface analysis, exploration of DNA binding, urease enzyme inhibition and anticancer activities of novel adamantane-naphthyl thiourea conjugate.

1-(adamantane-1-carbonyl-3-(1-naphthyl)) thiourea (C22H24N2OS (4), was synthesized by the reaction of freshly prepared adamantane-1-carbonyl chloride from corresponding acid (3) with ammonium thiocyanate in 1:1 M ratio in dry acetone to afford the adamantane-1-carbonyl isothiocyanate (2) in situ followed by treatment with 1-naphthyl amine (3). The structure was established by elemental analyses, FTIR, 1H, 13C NMR and mass spectroscopy. The molecular and crystal structure were determined by single crystal X-ray analysis. It belongs to triclinic system P - 1 space group with a = 6.7832(5) Å, b = 11.1810(8) Å, c = 13.6660(10) Å, α = 105.941(6)°, ß = 103.730(6)°, γ = 104.562(6)°, Z = 2, V = 910.82(11) Å3. The naphthyl group is almost planar. In the crystal structure, intermolecular CH···O hydrogen bonds link the molecules into centrosymmetric dimers, enclosing R22(14) ring motifs, while the intramolecular NH···O hydrogen bonds enclose S(6) ring motifs, in which they may be effective in the stabilization of the structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H … H (59.3%), H … C/C … H (19.8%) and H … S/S … H (10.1%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. DFT, molecular docking and urease inhibition studies revealed stability and electron withdrawing nature of 4 as compared to DNA base pairs and residues of urease. The DNA binding results from docking, UV- visible spectroscopy, and viscosity studies indicated significant binding of 4 with the DNA via intercalation and groove binding. Further investigation of the compound was done on hepatocellular carcinoma; Huh-7 cell line as well as normal human embryonic kidney; Hek-293 cell line. The compound showed significant cytotoxic activity against Huh-7 cells in comparison to normal Hek-293 cells indicating selective cytotoxicity towards cancer cells.

New aryl Schiff bases of thiadiazole derivative of ibuprofen as DNA binders and potential anticancer drug candidates.

The work presented in this paper describes the synthesis of two new aryl Schiff bases [(E)-N-(4-(benzyloxy)-3-methoxybenzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-1) and [(E)-N-(4-(benzyloxy)benzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-2). These compounds were characterized by different analytical techniques and then studied for DNA binding. Binding studies were carried out at neutral pH (7.0) and at 37 °C by theoretical and experimental methods including DFT, molecular docking, spectroscopy (UV-visible, fluorescence), cyclic voltammetry (CV) and viscometry. Further investigations of these compounds were done on hepatocellular carcinoma; Huh-7 cancer cell line. Binding constant, free energy change and binding site size, i.e. Kb, ΔG and n were evaluated which indicated that both ASB-1 and ASB-2 bind significantly and spontaneously with the DNA. However, data revealed relatively greater binding of ASB-1 with DNA. Spectral and voltammetric results were found supportive of each other. Binding site sizes and viscosity measurements verified the mixed binding mode of interactions as observed in molecular docking analysis, i.e. intercalation with groove binding. DNA binding studies were very well correlated with the in-vitro studies performed on Huh-7 cell line as well as normal HEK-293 cell lines. The compound ASB-1 not only showed greater binding affinity toward DNA but also showed greater anticancer potency with least IC50 value as compared to ASB-2.

Synthesis, X-ray crystal structure elucidation and Hirshfeld surface analysis of N-((4-(1H-benzo[d]imidazole-2-yl)phenyl)carbamothioyl)benzamide: investigations for elastase inhibition, antioxidant and DNA binding potentials for biological applications.

The interest in the present study pertains to the development of a new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, free radical scavenging activity and its DNA binding ability. The title compound, N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-3-benzoyl thiourea (C21H18N4O2SH2O:TUBC), was synthesized by reacting an acid chloride of benzoic acid with potassium thiocyanate (KSCN) along with the subsequent addition of 4-(1H-benzo[d]imidazol-2-yl)benzenamine via a one-pot three-step procedure. The structure of the resulting benzimidazole based thiourea was confirmed by spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR and single crystal X-ray diffraction and further examined by Hirshfeld surface analysis. TUBC was also investigated by using both in silico methodology including molecular docking for elastase inhibition along with quantum chemical studies and in vitro experimental methodology utilizing elastase inhibition and free radical scavenging assay along with DNA binding experiments. Docking results confirmed that TUBC binding was within the active region of elastase. In comparison to the reference drug oleanolic acid, the low IC50 value of TUBC also indicated its high tendency towards elastase inhibition. TUBC scavenged 80% of DPPH˙ radicals which pointed towards its promising antioxidant activity. TUBC-DNA binding by DFT, docking, UV-visible spectroscopy and viscosity measurements revealed TUBC to be a potential drug candidate that binds spontaneously and reversibly with DNA via a mixed binding mode. All theoretical and experimental findings pointed to TUBC as a potential candidate for a variety of biological applications.

Alternating Current Electrophoretic Deposition of Chitosan-Gelatin-Bioactive Glass on Mg-Si-Sr Alloy for Corrosion Protection.

Magnesium alloys have gained significant attention as degradable implant materials, but the fast and localized corrosion behavior leading to hydrogen gas evolution and alkaline poisoning limits their clinical application. In this research, the possibility of controlling the fast degradation rate of an experimental Mg-Si-Sr alloy by applying hybrid biopolymer chitosan (CS)-gelatin (G)-bioactive glass (BG) coatings was investigated. Electrophoretic deposition using alternating current fields (AC-EPD) was employed for surface coating and the influence of suspension parameters (biopolymer type and concentration, BG particle size), and key AC-EPD parameters (voltage amplitude, frequency, and time) on the coating quality were investigated. Stable suspensions of positively charged biopolymer/BG particles deposited on the Mg alloy coupled as a cathode during the high-amplitude peak. Furthermore, coating homogeneity improved with increasing peak-to-peak-voltage and the hybrid nature of the coatings was confirmed by scanning electron microscopy and Fourier transform infrared spectroscopy. Corrosion studies revealed a significantly decreased corrosion rate down to 0.08 mm/year for the Mg-Si-Sr alloy incorporating CS-G-BG b AC-EPD coating.

Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT, and DNA-Binding Studies of (E)-2-(3-Hydroxy-4-Methoxybenzylidene)Hydrazinecarbothioamide.

(E)-2-(3-Hydroxy-4-methoxybenzylidene)hydrazinecarbothioamide 3 was synthesized by reacting thiosemicarbazide with 2-hydorxy-3-methoxybenzaldehyde in dry ethanol. The structure was elucidated by spectroscopic (FT-IR, 1H NMR, and 13C NMR) and single crystal X-ray diffraction techniques. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces and their associated two-dimensional fingerprint plots. DFT, spectroscopic, and electrochemical DNA-binding analysis confirmed that the compound is reactive to bind with DNA. Viscometric studies suggested that compound 3 has a mixed mode of interaction and intercalated into the DNA base pairs predominantly along with the possibility of electrostatic interactions. Graphical Abstract.

Aroylthiourea derivatives of ciprofloxacin drug as DNA binder: Theoretical, spectroscopic and electrochemical studies along with cytotoxicity assessment.

Aroylthiourea derivatives of ciprofloxacin drug - [1-cyclopropyl-6-fluoro-7-(4-((4-methoxybenzoyl)carbamothioyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid] ATU-1, [1-cyclopropyl-7-(4-((2,4-dibromobenzoyl)carbamothioyl)piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid] ATU-2, and [1-cyclopropyl-7-(4-((3,5-dinitrobenzoyl)carbamothioyl)piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid] ATU-3 were synthesized, characterized and investigated for DNA binding at stomach pH (4.7) and at 37 °C. All findings by using DFT, molecular docking, spectroscopic (UV-, fluorescence; FL-), cyclic voltammetric (CV) and viscometric techniques revealed that these compounds have the potency to bind with DNA via a mixed mode of interaction. The binding affinity of ATU-1 was evaluated comparatively greater with Kb × 104/M-1 (docking; 5.55, UV-; 7.93, FL-; 5.62, CV; 6.06), ΔG/kJmol-1(docking; -27.07, UV-; -29.07, FL-; -28.18, CV; -28.38) and n (FL-; 1.20, CV; 2.72). Stern-Volmer quenching constant (Ksv) further pointed towards comparatively greater binding affinity of ATU-1 for DNA, while bimolecular quenching constant (Kq) values showed the involvement of static quenching mechanism in the compound - DNA interaction. Comparatively lesser IC50 (7.1 µM) value obtained from biological work on Huh-7 cancer cell line further confirmed the greater anticancer potential of ATU-1 than that of ATU-2&3.

Synthesis, theoretical, spectroscopic and electrochemical DNA binding investigations of 1, 3, 4-thiadiazole derivatives of ibuprofen and ciprofloxacin: Cancer cell line studies.

Two new 1,3,4-thiadiazole derivatives of ibuprofen and ciprofloxacin namely {(5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine)} 1 and {(3-(5-amino-1,3,4-thiadiazol-2-yl)-1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one)} 2 were synthesized and characterized by spectroscopic and elemental analysis. DFT and molecular docking were done initially for theoretical binding possibilities of the investigated compounds. In vitro DNA binding investigations were carried out with UV-visible spectroscopic, fluorescence spectroscopic, cyclic voltammetric (CV) experiments under physiological conditions of the stomach (4.7) and blood (7.4) pH and at normal body temperature (37 °C). Both theoretical and experimental results suggested spontaneous and significant intercalative binding of the compounds with DNA. Kinetic and thermodynamic parameters (Kb, ΔG) were evaluated greater for compound 2 which showed comparatively more binding and more spontaneity of 2 than 1 to bind with DNA at both pH values. Binding site sizes were found greater (n > 1) and revealed the possibility of other sites for interactions along with intercalation. Overall results for DNA binding were found more significant for 2 at Stomach (4.7) pH. Viscometric studies further verified intercalation as a prominent binding mode for both compounds. IC50 values obtained from human hepatocellular carcinoma (Huh-7) cell line studies revealed 2 as potent anticancer agent than 1 as value found 25.75 µM (lesser than 50 µM). Theoretical and experimental DNA binding studies showed good correlation with cancer cell (Huh-7) line activity of 1 and 2 and further suggested that these compounds could act as potential anti-cancer drug candidates.

Electrochemical, spectroscopic and theoretical monitoring of anthracyclines' interactions with DNA and ascorbic acid by adopting two routes: Cancer cell line studies.

Pharmacodynamic interactions of three anthracycline antibiotics namely doxorubicin (DXH), epirubicin (EpiDXH) and daunorubicin (DNR) with DNA in the absence and presence of ascorbic acid (AA) as natural additive were monitored under physiological conditions (pH = 7.4, 4.7 and T = 309.5K). Route-1 (Anthracycline-AA-DNA) and Route-2 (Anthracycline-DNA-AA) were adopted to see the interactional behavior by cyclic voltammetry (CV) and UV-visible spectroscopy. In comparison to Route-2; voltammetric and spectral responses as well as binding constant (Kb) and Gibb's free energy change (ΔG) values revealed strongest and more favorable interaction of anthracycline-AA complex with DNA via Route-1. Kb, s (binding site sizes) and ΔG evaluated from experimental (CV, UV-Vis) and theoretical (molecular docking) findings showed enhanced binding strength of tertiary complexes as compared to binary drug-DNA complexes. The results were found comparatively better at pH 7.4. Consistency was observed in binding parameters evaluated from experimental and theoretical techniques. Diffusion coefficients (Do) and heterogeneous electron transfer rate constant (ks,h) confirmed the formation of complexes via slow diffusion kinetics. Percent cell inhibition (%Cinh) of anthracyclines for non-small cell cancer cell lines (NSCCLs) H-1299 and H-157 were evaluated higher in the presence of AA which further complimented experimental and theoretical results.