Investigation of antileishmanial, antioxidant activities, CT-DNA interaction and DFT study of novel cobalt(II) complexes derived from mesogenic aromatic amino acids based Schiff base ligands.

In the present work, new Co(II) complexes were synthesized from mesogenic aromatic amino acids based Schiff base ligands, HL1 [Methyl 2-((2-hydroxy-4-(tetradecyloxy)benzylidene)amino)-3-phenylpropanoate] and HL2 [Methyl 2-((2-hydroxy-4-(tetradecyloxy)benzylidene)amino)-3-(1H-indol-2-yl)propanoate]. The compounds were thoroughly characterised using different elemental, thermogravimetric and spectroscopic studies. The in-vitro antileishmanial efficacy of the compounds against Leishmania donovani was evaluated by MTT assay and the antioxidant activity was performed by Mensor's method. The cell viability percentage and IC50 values for both the antileishmanial and antioxidant studies revealed that the cobalt(II) complexes are comparable to the standard, amphotericin B and ascorbic acid, respectively, signifying the potential applications of the biogenic compounds. The CT-DNA interaction experiments study using photophysical techniques indicated that the cobalt(II) complexes exhibited pronounced interactions as compared to the parent ligand. The parent ligands were found to possess mesogenicity as evidenced from the polarizing optical microscope (POM) and differential scanning calorimetry (DSC). The optical band gap of the compounds, as estimated from the Tauc plot of the UV-Vis spectra, lies within the domain of optoelectronic material properties, which was further supported through Density Functional Theory (DFT) study. Moreover, DFT methods have been used to explore the ground state geometry and DFT based reactivity descriptors of the two synthesised ligands, HL1 and HL2 along with their corresponding Co(II) complexes, Co(L1)2 and Co(L2)2. Reactivity descriptors obtained from Conceptual Density Functional Theory (CDFT) analysis reveal that Co(L1)2 is the most stable and Co(L2)2 is the most electrophilic.

Targeting HER2 in Gastroesophageal Adenocarcinoma: Molecular Features and Updates in Clinical Practice.

Gastroesophageal adenocarcinoma (GEA) is one of the principal causes of death related to cancer globally. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor which is found to be overexpressed or amplified in approximately 20% of GEA cases. In GEA, the identification of HER2-positive status is crucial to activate a specific anti-HER2 targeted therapy. The landmark ToGA trial demonstrated the superiority of adding trastuzumab to platinum-based chemotherapy, becoming the first-line standard of treatment. However, unlike breast cancer, the efficacy of other anti-HER2 drugs, such as lapatinib, pertuzumab, and T-DM1, has failed to improve outcomes in advanced and locally advanced resectable GEA. Recently, the combination of trastuzumab with pembrolizumab, along with chemotherapy, and the development of trastuzumab deruxtecan, with its specific bystander activity, demonstrated improved outcomes, renewing attention in the treatment of this disease. This review will summarise historical and emerging therapies for the treatment of HER2-positive GEA, with a section dedicated to the HER2 molecular pathway and the use of novel blood biomarkers, such as circulating tumour DNA and circulating tumour cells, which may be helpful in the future to guide treatment decisions.

Extensive natural Agrobacterium-induced transformation in the genus Camellia.

MAIN CONCLUSION: The genus Camellia underwent extensive natural transformation by Agrobacterium. Over a period of 15 million years, at least 12 different inserts accumulated in 72 investigated Camellia species. Like a wide variety of other wild and cultivated plants, Camellia species carry cellular T-DNA sequences (cT-DNAs) in their nuclear genomes, resulting from natural Agrobacterium-mediated transformation. Short and long DNA sequencing reads of 435 accessions belonging to 72 Camellia species (representing 12 out of 14 sections) were investigated for the occurrence of cT-DNA insertions. In all, 12 different cT-DNAs were recovered, either completely or partially, called CaTA to CaTL. Divergence analysis of internal cT-DNA repeats revealed that the insertion events span a period from 0.075 to 15 Mio years ago, and yielded an average transformation frequency of one event per 1.25 Mio years. The two oldest inserts, CaTA and CaTD, have been modified by spontaneous deletions and inversions, and by insertion of various plant sequences. In those cases where enough accessions were available (C. japonica, C. oleifera, C. chekiangoleosa, C. sasanqua and C. pitardii), the younger cT-DNA inserts showed a patchy distribution among different accessions of each species, indicating that they are not genetically fixed. It could be shown that Camellia breeding has led to intersectional transfer of cT-DNAs. Altogether, the cT-DNAs cover 374 kb, and carry 47 open reading frames (ORFs). Two Camellia cT-DNA genes, CaTH-orf358 and CaTK-orf8, represent new types of T-DNA genes. With its large number of cT-DNA sequences, the genus Camellia constitutes an interesting model for the study of natural Agrobacterium transformants.

Antimicrobial screening involving Helicobacter pylori of nano-therapeutic compounds based on the amoxicillin antibiotic drug.

Nano-structure Cu(II) complex [Cu(AMAB)2 ]Cl2 with Schiff base (AMAB) derived from the condensation between 4-(dimethylamino)benzaldehyde and amoxicillin trihydrate was prepared. (AMAB) Schiff base and its Cu(II) complex were identified and confirmed by different physicochemical techniques. The Schiff base (AMAB) was coordinated to copper ion through carbonyl oxygen and imine nitrogen donor sites. X-ray powder diffraction shows a cubic crystal system of the Cu(II) complex. The density functional theory was used to optimize the structure geometries of the investigated compounds. The molecular docking of the active amino acids of the investigated proteins' interactions with the tested compounds was evaluated. The bactericidal or bacteriostatic effect of the compounds was screened against some bacterial strains. The activity of Cu-chelate against Gram-negative bacteria was mainly more effective than its (AMAB) ligand and vice versa in the case of Gram-positive bacteria. The biological activity of the prepared compounds with biomolecules calf thymus DNA (CT-DNA) was determined by electronic absorption spectra and DNA gel electrophoresis technique. All studies revealed that the Cu-chelate derivative exhibited better binding affinity to both CT-DNA than the AMAB and amoxicillin itself. The anti-inflammatory effect of the designed compounds was determined by testing their protein denaturation inhibitory activity spectrophotometrically. All obtained data supported that the designed nano-Cu(II) complex with Schiff base (AMAB) is a potent bactericide against H. pylori, and exhibits anti-inflammatory activity. The dual inhibition effects of the designed compound represent a modern therapeutic approach with extended spectrum of action. Therefore, it can act as good drug target in antimicrobial and anti-inflammtory therapies. Finally, H. pylori resistance to amoxicillin is absent or rare in many countries, thus amoxicillin nanoparticles may be beneficial for countries where amoxicillin resistance is reported.

Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand?

The therapeutic landscape in locally advanced rectal cancer (LARC) has undergone a significant paradigm shift in recent years with the rising adoption of total neoadjuvant treatment (TNT). This comprehensive approach entails administering chemotherapy and radiation therapy before surgery, followed by optional adjuvant chemotherapy. To establish and deliver the optimal tailored treatment regimen to the patient, it is crucial to foster collaboration among a multidisciplinary team comprising healthcare professionals from various specialties, including medical oncology, radiation oncology, surgical oncology, radiology, and pathology. This review aims to provide insights into the current state of TNT for LARC and new emerging strategies to identify potential directions for future research and clinical practice, such as circulating tumor-DNA, immunotherapy in mismatch-repair-deficient tumors, and nonoperative management.

New N4-Donor Ligands as Supramolecular Guests for DNA and RNA: Synthesis, Structural Characterization, In Silico, Spectrophotometric and Antimicrobial Studies.

The present work reports the synthesis of new N4-donor compounds carrying p-xylyl spacers in their structure. Different Schiff base aliphatic N-donors were obtained synthetically and subsequently evaluated for their ability to interact with two models of nucleic acids: calf-thymus DNA (CT-DNA) and the RNA from yeast Saccharomyces cerevisiae (herein simply indicated as RNA). In more detail, by condensing p-xylylenediamine and a series of aldehydes, we obtained the following Schiff base ligands: 2-thiazolecarboxaldehyde (L1), pyridine-2-carboxaldehyde (L2), 5-methylisoxazole-3-carboxaldehyde (L3), 1-methyl-2-imidazolecarboxaldehyde (L4), and quinoline-2-carboxaldehyde (L5). The structural characterisation of the ligands L1-L5 (X-ray, 1H NMR, 13C NMR, elemental analysis) and of the coordination polymers {[CuL1]PF6}n (herein referred to as Polymer1) and {[AgL1]BF4}n, (herein referred to as Polymer2, X-ray, 1H NMR, ESI-MS) is herein described in detail. The single crystal X-ray structures of complexes Polymer1 and Polymer2 were also investigated, leading to the description of one-dimensional coordination polymers. The spectroscopic and in silico evaluation of the most promising compounds as DNA and RNA binders, as well as the study of the influence of the 1D supramolecular polymers Polymer1 and Polymer2 on the proliferation of Escherichia coli bacteria, were performed in view of their nucleic acid-modulating and antimicrobial applications. Spectroscopic measurements (UV-Vis) combined with molecular docking calculations suggest that the thiazolecarboxaldehyde derivative L1 is able to bind CT-DNA with a mechanism different from intercalation involving the thiazole ring in the molecular recognition and shows a binding affinity with DNA higher than RNA. Finally, Polymer2 was shown to slow down the proliferation of bacteria much more effectively than the free Ag(I) salt.

Time-resolved emission spectroscopy to elucidate the functional nature of heat-stable transcription factor.

A 22 kDa protein from Thermus thermophilus is characterised as a DNA binding transcription regulator and its function is established using the fluorescence spectroscopy technique. The steady-state fluorescence spectroscopy result shows significant binding of calf thymus DNA and protein molecule. To confirm, the DNA quenching effect in real-time, a time-resolved emission spectroscopy study was performed and the result shows good agreement with steady-state quenching analysis.

Evaluation of the binding effect and cytotoxicity assay of 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione on calf thymus DNA: spectroscopic, calorimetric, and molecular dynamics approaches.

With advances in new drug therapies, it is essential to understand the interactions between drugs and target molecules. In this study, we applied multiple spectroscopic techniques including absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, calorimetric, and molecular dynamics (MD) simulation to study the interaction between 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione (PPF) and calf thymus DNA (ct DNA) in the absence or presence of histone H1. PPF exhibits a high binding affinity towards ct DNA in binary and ternary systems. In addition, the result for the binding constant was observed within the range 104 M-1 achieved through fluorescence quenching data, while the values for enthalpy and entropy changes for ct DNA-PPF and (ct DNA-H1) PPF complexes were measured to be -72.54 kJ.mol-1 , -161.14 J.mol-1  K-1 , -85.34 kJ.mol-1 , and -19.023 J.mol-1  K-1 , respectively. Furthermore, in accordance with circular dichroism spectra, the inducement of ct DNA structural changes was observed during binding of PPF and H1 in binary and ternary system forms. The essential roles of hydrogen bonding and van der Waals forces throughout the interaction were suggested using thermodynamic parameters. According to the obtained data, the interaction mode of ct DNA-PPF and (ct DNA-H1) PPF complexes was intercalation binding. Suggested by the MD simulation study, the ct DNA-H1 complex caused a reduction in the stability of the DNA structure in the presence or absence of ligand, which demonstrated that PPF as an intercalating agent can further distort the structure. The information achieved from this study will be very helpful in understanding the effects of PPF on the conformational state of ct DNA in the absence or presence of the H1 molecule, which seems to be quite significant for clarifying the mechanisms of action and its pharmacokinetics.

Ru(II)(ƞ6-p-cymene) Conjugates Loaded onto Graphene Oxide: An Effective pH-Responsive Anticancer Drug Delivery System.

Graphene oxide-based nanodrug delivery systems are considered one of the most promising platforms to deliver therapeutic drugs at the target site. In this study, Ru(II)(ƞ6-p-cymene) complexes containing the benzothiazole ligand were covalently anchored on graphene oxide using the ultrasonication method. The nanoconjugates GO-NCD-1 and GO-NCD-2 were characterized by FT-IR, UV-visible, 1H NMR, TGA, SEM, and TEM techniques, which confirmed the successful loading of both the complexes (NCD 1 and NCD 2) on the carrier with average particle diameter sizes of 17 ± 6.9 nm and 25 ± 6.5 nm. In vitro DNA binding studies of the nanoconjugates were carried out by employing various biophysical methods to investigate the binding interaction with the therapeutic target biomolecule and to quantify the intrinsic binding constant values useful to understand their binding affinity. Our results suggest (i) high Kb and Ksv values of the graphene-loaded conjugates (ii) effective cleavage of plasmid DNA at a lower concentration of 7.5 µM and 10 µM via an oxidative pathway, and (iii) fast release of NCD 2 at an acidic pH that could have a good impact on the controlled delivery of drug. It was found that 90% of the drug was released in an acidic pH (5.8 pH) environment in 48 h, therefore suggesting pH-responsive behavior of the drug delivery system. Molecular docking, DFT studies, and cytotoxicity activity against three cancer cell lines by SRB assay were also performed.

Circulating Tumor DNA-Based Testing and Actionable Findings in Patients with Advanced and Metastatic Pancreatic Adenocarcinoma.

PURPOSE: Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. MATERIALS AND METHODS: From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. RESULTS: All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. CONCLUSION: Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. IMPLICATIONS FOR PRACTICE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.

Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies.

N-formyl pyrazoline derivatives (3a-3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV-visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a-3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a-3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure-function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a-3l) was examined by relaxation assay at varying concentrations 100-1000 µM.

Synthesis, spectral characterization, DFT calculations, pharmacological studies, CT-DNA binding and molecular docking of potential N, O-multidentate chelating ligand and its VO(II), Zn(II) and ZrO(II) chelates.

The pharmacological efficacy of the variety tetradentate ligands encouraged us to design attractive compounds through effective synthetic procedure. The prepared Schiff base ligand 6,6'-((1E,1'E)-((4-chloro-1,2-phenylene)bis(azaneylylidene))bis(methaneylylidene))bis(2-ethoxy phenol (H2L), which derived from 4-chloro-o-phenylenediamine and 3-ethoxy-salicylaldehyde and its VO(II), Zn(II) and ZrO(II) metal chelates, have been synthesized and characterized with aim of that it may struggle the invasion of drug resistance. The chemical structural of studied compounds were discussed by TGA, elemental analysis, UV-Vis., 1H NMR, 13C NMR, FTIR, mass spectral, PXRD, molar conductance, magnetic susceptibility measurements and density functional theory. The results assigned square pyramid geometries for [VOL] and [ZrOL].2H2O chelates and an octahedral geometry for [ZnL(H2O)2].2H2O chelate. Powder XRD data showed that the complexes are monoclinic with polycrystalline nature. The results of CT-DNA interaction with the titled chelates showed that the binding between CT-DNA and the metal complexes occurs through intercalation mode. Their CT-DNA binding efficiency estimated in terms of their binding constants (Kb), which gave the order: VOL (6.9 × 105) > ZrOL (6.3 × 105) > ZnL(H2O)2 (5.5 × 105). The antimicrobial activities of the synthesized compounds were tested against selected fungal and bacterial strains using well diffusion technique. The obtained chelates showed higher antifungal and antibacterial activities than their corresponding ligand. Furthermore, the M-complexes showed higher potent cytotoxic effect toward HEK-293, human colorectal HepG-2, HCT-116 and MCF-7 adenocarcinoma cell lines compared to the free H2L ligand. Investigation of antioxidant property represented that all the prepared complexes have better radical scavenging potencies against DPPH radicals than the free H2L ligand. To study the molecular docking of proposed compounds versus Tyrosine kinases receptor (TKR), we used AutoDock1.5.6rc3® suite. The current compounds (H2L, VOL, ZrOL and ZnL(H2O)2) and STI were found to bind with C-kit of TKR with HBs at ILE789.A, ILE808.A, ASP810.A, GLU640.A and TYR846 amino acid residue and the binding energies were - 8.9, -8.93, -8.83, -1.48 and -10.39 kcal/mol respectively.

Molecular interaction studies of zinc sulphide nanoparticles with DNA and its consequence: a multitechnique approach.

Molecular interaction studies between nanoparticles (NPs) and biomolecules are of great importance in the field of nanomedicine as they affect many physiological processes. Therefore, the interaction of zinc sulphide nanoparticles (ZnS NPs) with calf thymus deoxyribonucleic acid (CT DNA) and its significance was analyzed using ultraviolet (UV)-visible light, fluorescence, circular dichroism (CD), zeta potential, viscometry, electrochemical, and polymerase chain reaction methods. Fluorescence quenching analysis revealed that the fluorescence of ZnS NPs was quenched using CT DNA through a static quenching mechanism. The negative values of thermodynamic parameters (ΔG, ΔH, and ΔS) showed that the binding process was spontaneous, exothermic, and van der Waals or hydrogen bonding plays an important role in the interaction of ZnS NPs with CT DNA. Thermal melting (Tm ) studies indicated a decrease in the Tm of CT DNA, suggesting the destabilization of CT DNA upon interaction with ZnS NPs. In addition, the results obtained from competitive binding, zeta potential, CD, and viscometry measurements showed that the interaction of ZnS NPs with CT DNA is through groove binding. Electrochemical analysis further confirmed the observed results from various spectroscopic and other related studies, in which decrease in the redox peak current along with changes in peak potential (CV) and increase in the electrical resistance (EIS) indicated the interaction between ZnS NPs and CT DNA. Furthermore, PCR analysis using DNA polymerase revealed the potential of ZnS NPs to inhibit DNA replication in vitro. ZnS NP-CT DNA interaction studies can be explored to define new horizons in biomedical applications of ZnS NPs.

Synthesis, structural characterization, and biological studies of ATBS-M complexes (M(II) = Cu, Co, Ni, and Mn): Access for promising antibiotics and anticancer agents.

A new bidentate Schiff base ligand (ATBS [4-bromo-2-(thiazole-2-yliminomethyl)phenol]) was synthesized via the condensation reaction of 2-aminothiazole with 5-bromosalicylaldehyde in ethanol. The reaction of ATBS with transition metal salts of Cu(II), Co(II), Ni(II), and Mn(II) afforded the corresponding ATBS-M complexes. Results from physicochemical and spectral analyses, such as elemental analysis, infrared, UV-Vis spectroscopy, magnetic susceptibility, and molar conductance, revealed a nonelectrolytic nature with octahedral (Oh ) geometry and a metal/ligand ratio of 1:2 for Cu(II), Co(II), and Ni(II), but 1:1 for the Mn(II) complex. The density functional theory (DFT) calculations are correlated very well with the proposed structure and molecular geometry of the complexes as [M(ATBS)2 ] (M = Cu, Co, and Ni) and [Mn(ATBS)(H2 O)2 ]. Significantly, the prepared compounds showed strong inhibition activity for a wide spectrum of bacteria (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus) and fungi (Candida albicans, Aspergillus flavus, and Trichophyton rubrum), with the ATBS-Ni complex being the most promising antibiotic agent. Molecular docking studies of the binding interaction between the title complexes with the bacterial protein receptor CYP51 revealed clear insights about the inhibition nature against the studied microorganisms, with the following order: ATBS-Cu > ATBS-Mn > ATBS-Ni > ATBS-Co for complex stability. Moreover, the cytotoxicity measurements of all prepared metal complexes against the colon carcinoma (HCT-116) and hepatocellular carcinoma (Hep-G2) cell lines showed exceptional anticancer efficacy of the complexes as compared with the free ATBS Schiff base ligand. Significantly, the results attested that ATBS-Cu is the most effective complex against HCT-116 cells, whereas ATBS-Mn has the highest cytotoxic efficiency against Hep-G2 cells. Furthermore, electronic spectra, viscosity measurements, and gel electrophoresis techniques were employed to probe the interaction of all prepared ATBS-metal complexes with calf thymus (CT)-DNA. Results confirmed that all complexes are strongly bound to CT-DNA via intercalation mode, with the ATBS-Co complex having the highest binding ability.

Stimulation of Sulfonamides Antibacterial Drugs Activity as a Result of Complexation with Ru(III): Physicochemical and Biological Study.

Antibiotic resistance is a global problem, and one promising solution to overcome this issue is using metallodrugs, which are drugs containing metal ions and ligands. These complexes are superior to free ligands in various characteristics including anticancer properties and mechanism of action. The pharmacological potential of metallodrugs can be modulated by the appropriate selection of ligands and metal ions. A good example of proper coordination is the combination of sulfonamides (sulfamerazine, sulfathiazole) with a ruthenium(III) ion. This work aimed to confirm that the activity of sulfonamides antibacterial drugs is initiated and/or stimulated by their coordination to an Ru(III) ion. The study determined the structure, electrochemical profile, CT-DNA affinity, and antimicrobial as well as anticancer properties of the synthesized complexes. The results proved that Ru(III) complexes exhibited better biological properties than the free ligands.

Quinoline Functionalized Schiff Base Silver (I) Complexes: Interactions with Biomolecules and In Vitro Cytotoxicity, Antioxidant and Antimicrobial Activities.

A series of fifteen silver (I) quinoline complexes Q1-Q15 have been synthesized and studied for their biological activities. Q1-Q15 were synthesized from the reactions of quinolinyl Schiff base derivatives L1-L5 (obtained by condensing 2-quinolinecarboxaldehyde with various aniline derivatives) with AgNO3, AgClO4 and AgCF3SO3. Q1-Q15 were characterized by various spectroscopic techniques and the structures of [Ag(L1)2]NO3Q1, [Ag(L1)2]ClO4Q6, [Ag(L2)2]ClO4Q7, [Ag(L2)2]CF3SO3Q12 and [Ag(L4)2]CF3SO3Q14 were unequivocally determined by single crystal X-ray diffraction analysis. In vitro antimicrobial tests against Gram-positive and Gram-negative bacteria revealed the influence of structure and anion on the complexes' moderate to excellent antibacterial activity. In vitro antioxidant activities of the complexes showed their good radical scavenging activity in ferric reducing antioxidant power (FRAP). Complexes with the fluorine substituent or the thiophene or benzothiazole moieties are more potent with IC50 between 0.95 and 2.22 mg/mL than the standard used, ascorbic acid (2.68 mg/mL). The compounds showed a strong binding affinity with calf thymus-DNA via an intercalation mode and protein through a static quenching mechanism. Cytotoxicity activity was examined against three carcinoma cell lines (HELA, MDA-MB231, and SHSY5Y). [Ag(L2)2]ClO4Q7 with a benzothiazole moiety and [Ag(L4)2]ClO4Q9 with a methyl substituent had excellent cytotoxicity against HELA cells.

Some novel rare earth metal ions complexes: Synthesis, characterization, luminescence and biocidal efficiency.

New lanthanide complexes (1-3) of the general formulae [Ln(L)(NO3)(H2O)] have been synthesized by reaction of Ln(NO3)3 {Ln = La (1), Sm (2) and Yb (3)} with 2,2'-(((1E,1'E)-thiophene-2,5-diylbis(methaneylylidene))bis(azaneylylidene))diphenol (H2L). Based on elemental analysis, spectroscopic studies (UV-Vis., FT-IR, ESI-MS, 1H/13C NMR), molar conductance and thermogravimetric analysis, the Schiff base ligand was suggested to coordinate Ln(III) ions through the azomethine nitrogens, deprotonated hydroxyl groups, and thiophene sulphur atom. The interaction of the synthetic compounds with CT-DNA has been studied by the electronic spectroscopy, fluorometric competition studies with ethidium bromide and DNA viscosity measurements. Furthermore, due to the ligand and its Ln(III) complexes exhibit good DNA binding affinity, it is considered worthwhile to investigate their antioxidant activity. The data have shown that, the complexes are more effective inhibitors towards reactive oxygen species (ROS), such as superoxide anion and hydroxyl radical. The activity of test compounds in ascending order (1) > (2) > (3) > H2L in terms of IC50 value. The anticancer activities of the complexes have also been studied towards human colon carcinoma cancer (HCT-116) and human breast cancer (MCF-7) cell lines.

Structural motives controlling the binding affinity of 9,10-bis(methylpyridinium)anthracenes towards DNA.

In the search of new DNA groove binding agents a series of substituted 9,10-methylpyridiniumanthracenes have been synthesized and their interactions with DNA have been studied by UV/vis absorption, CD and fluorescence spectroscopy. A minor groove binding mode is confirmed by DNA melting studies, strong CD effects, the dependence of the binding affinity on ionic strength, and the differentiation between AT and GC base pairs. No binding occurs to GC sequences. Binding constants to calf thymus DNA (ct-DNA) and poly(dA:dT) in the range between 1 × 104 and 3 × 105 M-1 have been determined. The binding strength decreases with the size of substituents attached at the anthracene site. Variation of the substitution pattern of the charged groups shows that methyl groups in meta position cause slightly stronger binding than methyl groups in para position. In contrast, with these groups in ortho position, no binding interaction has been observed. The strongest binding is achieved with an expansion of the peripheral heterocycle from pyridine to quinoline. Molecular modeling reveals the pivotal role of the substitution pattern: Anthracenes with para and meta pyridines align along the minor grooves. On the other hand, the ortho derivative adopts no groove-alignment.

Copper (II)-based halogen-substituted chromone antitumor drug entities: Studying biomolecular interactions with ct-DNA mediated by sigma hole formation and cytotoxicity activity.

Copper-based antitumor drug entities 1-3 derived from substituted (F-, Br-, -CH3) 3-formylchromone pharmacophore were synthesized and thoroughly characterized by spectroscopic and single X-ray crystallographic studies. These complexes show structural novelty due to presence of the X-bonds in chromone scaffold which could facilitate higher propensity for nucleic acids via sigma σ-hole interactions. Therefore, structure-activity relationship of 1-3 was studied by performing ct-DNA binding, pBR322 cleavage and cytotoxicity activity to validate their potential to act as chemotherapeutic drug entities. The binding studies of 1-3 with ct- DNA were carried out employing many biophysical techniques and the corroborative results of these experiments showed intercalation mode of binding and the order of binding was found to be 2 > 1 > 3. The structure of drug entities could facilitated strong halogen bonding interaction (in case of 1 &2) and stability of X bond was rationalized by sigma hole region of positive electrostatic potential on the surface of C-X covalent bond, as determined by gas phase B3LYP computational DFT studies. Interestingly, 2 exhibited most avid binding affinity due to presence of Br- electron withdrawing and polarizable group. Further, cleavage studies of 1-3 with pBR322 plasmid DNA were performed which demonstrated significant cleavage activity, the supercoiled form (Form I) of plasmid DNA was converted to nicked form (Form II) with the appearance of linearized form (Form III) in between two, implicating lethal double strand breaks of DNA. 2 showed predominantly higher cleavage activity following the similar trend as observed for binding studies. The cytotoxicity of the complexes 1-3 was evaluated by MTT assay against the human liver carcinoma (Huh-7) and prostate cancer (DU-145) cell lines; complex 2 exhibited specific and selective cytotoxicity for the DU-145 cancer cell line with LC50 value of 1.6 µM.

Synthesis of naphthalimide-phenanthro[9,10-d]imidazole derivatives: In vitro evaluation, binding interaction with DNA and topoisomerase inhibition.

The synthesis and characterization of a series of naphthalimide and phenanthro[9,10-d]imidazole conjugate is described. These compounds are evaluated in vitro for their cytotoxicity towards 60 human cancer cell lines. Derivative 16 shows excellent cytotoxic activity against these cancer cell lines with the range of growth inhibition from -55.78 to 94.53. The most potent derivative (ethylpiperazine, 16) is further studied to evaluate the interaction with ct-DNA using absorption and emission spectroscopy as well as DNA viscosity measurement. The DNA binding studies indicate that compound 16 is significantly interacted with DNA through groove binding having binding constant value of 7.81 × 104 M-1 alongwith partial intercalation between the base pairs of DNA strands. Further, topoisomerase inhibition study suggests that compound 16 is induced apoptosis and inhibits human topoisomerase (Topo-IIα) as a possible intracellular target. Molecular docking study of compound 16 with ct-DNA shows good docking score.