Anvarbatcha Riyasdeen

Mixed ligand copper(II) complexes of 1,10-phenanthroline with tridentate phenolate/pyridyl/(benz)imidazolyl Schiff base ligands: covalent vs non-covalent DNA binding, DNA cleavage and cytotoxicity.

A series of copper(II) complexes of the types [Cu(L)(phen)](ClO4) 1-2, where HL is a tridentate ligand with two nitrogen and one oxygen donor atoms (2NO) such as 2-(2-(1H-benzimidazol-2-yl)ethyliminomethyl)phenol (HL1) and 2-(2-(1H-benzimidazol-2-yl)ethyl-imino)methyl)-4-methylphenol (HL2), phen is 1,10-phenanthroline and [Cu(L)(phen)](ClO4)23-6, where L is a tridentate ligand with three nitrogen donor atoms (3N) such as (2-pyridin-2-ylethyl)pyridin-2-ylmethyleneamine (L3), 2-(1H-benzimidazol-2-yl)ethyl)-pyridin-2-yl-methyleneamine (L4), 2-(1H-benzimidazol-2-yl)ethyl)(1H-imidazol-2-ylmethylene)-amine (L5) and 2-(1H-benzimidazol-2-yl)ethyl)(4,4a-dihydroquinolin-2-ylmethylene)amine (L6), has been isolated and characterized by different spectral techniques. In single crystal X-ray structures, 1 possesses square pyramidal distorted trigonal bipyramidal (SPDTBP), geometry whereas 3 and 4 possess trigonal bipyramidal distorted square pyramidal (TBDSP) geometry. UV-Vis and fluorescence spectral studies reveal that the complexes 1-6 bind non-covalently to calf thymus DNA more strongly than the corresponding covalently bound chlorido complexes [Cu(2NO)Cl] 1a-2a and [Cu(3N)Cl2] 3a-6a. On prolonged incubation, all the complexes 1-6 exhibit double strand cleavage of supercoiled (SC) plasmid DNA in the absence of an activator. Also, they exhibit cytotoxicity against human breast cancer cell lines (HBL-100) more potent than their corresponding chlorido complexes 1a-6a, and have the potential to act as efficient cytotoxic drugs.

DNA/RNA binding and anticancer/antimicrobial activities of polymer-copper(II) complexes.

Water soluble polymer-copper(II) complexes with various degrees of coordination in the polymer chain were synthesized and characterized by elemental analysis, IR, UV-visible and EPR spectra. The DNA/RNA binding behavior of these polymer-copper(II) complexes was examined by UV-visible absorption, emission and circular dichroism spectroscopic methods, and cyclic voltammetry techniques. The binding of the polymer-copper(II) complexes with DNA/RNA was mainly through intercalation but some amount of electrostatic interaction was also observed. This binding capacity increased with the degree of coordination of the complexes. The polymer-copper(II) complex having the highest degree of coordination was subjected to analysis of cytotoxic and antimicrobial properties. The cytotoxicity study indicated that the polymer-copper(II) complexes affected the viability of MCF-7 mammary carcinoma cells, and the cells responded to the treatment with mostly through apoptosis although a few cells succumbed to necrosis. The antimicrobial screening showed activity against some human pathogens.

Human serum albumin binding and cytotoxicity studies of surfactant–cobalt(III) complex containing 1,10-phenanthroline ligand

The characteristics of the binding reaction of surfactant-cobalt(III) complex, cis-[Co(phen)₂(C₁₄H₂₉NH₂)]Cl₂·3H₂O (phen=1,10-phenanthroline, C₁₄H₂₉NH₂=tetradecylamine) with human serum albumin (HSA) were studied by fluorescence and UV-vis absorption spectroscopy. In addition, the effect of the surfactant-cobalt(III) complex on the conformation of HSA was analysed using synchronous fluorescence spectroscopy. The experimental results showed that surfactant-cobalt(III) complex caused the fluorescence quenching of HSA through a combination of static and dynamic quenching. The number of binding sites (n) and apparent binding constant (K(a)) of surfactant-cobalt(III) complex (above and below the critical micelle concentration (cmc) were determined at various temperatures. According to the thermodynamic parameters, it is likely that hydrophobic interactions are involved in the binding process. The cancer chemotherapeutic potential of surfactant-cobalt(III) complex on ME-180 cervical cancer cell was determined using MTT assay and specific staining techniques. The complex affected the viability of the cells significantly and the cells succumbed through an apoptosis process as seen in the nuclear morphology and cytoplasmic features. In addition, single-cell electrophoresis indicated DNA damage.

Surfactant–copper(II) Schiff base complexes: synthesis, structural investigation, DNA interaction, docking studies, and cytotoxic activity

A series of surfactant–copper(II) Schiff base complexes (1–6) of the general formula, [Cu(sal-R2)2] and [Cu(5-OMe-sal-R2)2], {where, sal = salicylaldehyde, 5-OMe-sal = 5-methoxy- salicylaldehyde, and R2 = dodecylamine (DA), tetradecylamine (TA), or cetylamine (CA)} have been synthesized and characterized by spectroscopic, ESI-MS, and elemental analysis methods. For a special reason, the structure of one of the complexes (2) was resolved by single crystal X-ray diffraction analysis and it indicates the presence of a distorted square-planar geometry in the complex. Analysis of the binding of these complexes with DNA has been carried out adapting UV-visible-, fluorescence-, as well as circular dichroism spectroscopic methods and viscosity experiments. The results indicate that the complexes bind via minor groove mode involving the hydrophobic surfactant chain. Increase in the length of the aliphatic chain of the ligands facilitates the binding. Further, molecular docking calculations have been performed to understand the nature as well as order of binding of these complexes with DNA. This docking analysis also suggested that the complexes interact with DNA through the alkyl chain present in the Schiff base ligands via the minor groove. In addition, the cytotoxic property of the surfactant–copper(II) Schiff base complexes have been studied against a breast cancer cell line. All six complexes reduced the visibility of the cells but complexes 2, 3, 5, and 6 brought about this effect at fairly low concentrations. Analyzed further, but a small percentage of cells succumbed to necrosis. Of these complexes (6) proved to be the most efficient aptotoxic agent.

Polyethyleneimine anchored copper(II) complexes: Synthesis, characterization, in vitro DNA binding studies and cytotoxicity studies

The water soluble polyethyleneimine-copper(II) complexes, [Cu(phen)(L-tyr)BPEI]ClO4 (where phen=1,10-phenanthroline, L-tyr=L-tyrosine and BPEI=branched polyethyleneimine) with various degree of copper(II) complex units in the polymer chain were synthesized and characterized by elemental analysis and electronic, FT-IR, EPR spectroscopic techniques. The binding of these complexes with CT-DNA was studied using UV-visible absorption titration, thermal denaturation, emission, circular dichroism spectroscopy and cyclic voltammetric methods. The changes observed in the physicochemcial properties indicated that the binding between the polymer-copper complexes and DNA was mostly through electrostatic mode of binding. Among these complexes, the polymer-copper(II) complex with the highest degrees of copper(II) complex units (higher degrees of coordination) showed higher binding constant than those with lower copper(II) complex units (lower degrees of coordination) complexes. The complex with the highest number of metal centre bound strongly due to the cooperative binding effect. Therefore, anticancer study was carried out using this complex. The cytotoxic activity for this complex on MCF-7 breast cancer cell line was determined adopting MTT assay, acridine orange/ethidium bromide (AO/EB) staining and comet assay techniques, which revealed that the cells were committed to specific mode of cell death either apoptosis or necrosis.

Antiproliferative and apoptosis-induction studies of a metallosurfactant in human breast cancer cell MCF-7

The cytotoxic potential of the surfactant–cobalt(III) complex (metallosurfactant) cis-[Co(trien)(C14H29NH2)Cl](ClO4)2 was tested on the MCF-7 breast cancer cell. The viability of the treated cell was evaluated by adopting MTT assay. The mode of cell death was assessed by adopting different morphological, cellular and molecular methods such as comet assay for DNA damage and apoptosis assays (Hoechst staining, acridine orange & ethidium bromide (AO & EB) staining and Annexin V-Cy3 assay). Mitochondria-mediated apoptosis was tested using JC-1 dye. Cell cycle analysis was made by adopting flow cytometry, and the expression of some key pro- and anti-apoptotic proteins was analyzed by adopting Western blotting. The surfactant–cobalt(III) complex induced cell death in a dose- and time-dependent manner. The mode of cell death was essentially apoptosis though necrosis was also noticed. Flow cytometric analysis indicated that the treatment caused cell cycle arrest, as indicated in the accumulation of cells in the sub-G0 + G1 compartment. Western blot analysis revealed the up-regulation of pro-apoptotic p53 and Bax proteins and down-regulation of anti-apoptotic Bcl-2 protein. The study revealed the antiproliferative and apoptosis-induction properties of the surfactant–cobalt(III) complex in an MCF-7 breast cancer cell, primarily by inducing DNA damage and possibly through elevation of ROS levels.

Antiproliferative property of n-hexane and chloroform extracts of Anisomeles malabarica (L). R. Br. in HPV16-positive human cervical cancer cells.

Objectives: To find the efficacy of serial extracts of Anisomeles malabarica in inhibiting proliferation of and inducing apoptosis in human cervical cancer cells, SiHa and ME 180, that are HPV 16-positive. Materials and Methods: The whole plant was extracted in n-hexane, chloroform, ethyl acetate, n-butanol, methanol, and water. The cells were treated with the extracts at increasing concentrations to find the IC50, adopting MTT ([3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]) assay. Acridine orange (AO) and ethidium bromide (EB) and Hoechst 33258 staining were adopted to assess the mode of cell death, Annexin V-Cy3 staining to evaluate one of the early apoptotic features, JC-1 staining to assess the mitochondrial membrane depolarization, comet assay for DNA fragmentation, and cell cycle analysis for the distribution of cells after treatment. Results: n-Hexane and chloroform extracts were cytotoxic to the cervical cancer cells in dose- and duration-dependent manner. The cells that responded to the treatments revealed typical apoptotic features. Early features of apoptosis, phosphatidyl serine translocation and loss of mitochondrial trans-membrane potential, were observed in the treated cells, and comet assay revealed DNA damage. In the FACS analysis, the cells accumulated in the sub-G0/G1 phase of the cell cycle, except in n-hexane- and chloroform extract–treated SiHa cells at 24 h, which showed arrest in S- and G2/M phases. Conclusions: n-Hexane and chloroform extracts of A. malabarica inhibit proliferation of and induce death in HPV16-positive cervical cancer cells, mostly by apoptosis and to some extent by necrosis.

Micellization Behaviour, DNA Binding, Antimicrobial, and Cytotoxicity Studies of Surfactant-Cobalt(III) Complexes Containing Di-and Tetramine Ligands

A new class of surfactant–cobalt(iii) complexes, cis-[Co(en)2(C11H23NH2)Cl](ClO4)2 (1), (en = ethylenediamine) and cis-[Co(trien)(C11H23NH2)Cl](ClO4)2 (2) (trien = triethylenetetramine) have been synthesized and characterized by UV/Vis, IR, 1H NMR, and 13C NMR spectroscopic methods and elemental and metal analysis. The critical micelle concentration (CMC) values of these surfactant–cobalt(iii) complexes in aqueous solution were obtained from conductance measurements. The specific conductivity data (at 298, 308, 318, and 328 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (ΔGm0, ΔHm0, and ΔSm0). Absorption spectroscopy, emission spectroscopy, and viscosity measurements have been used to investigate the binding of these complexes with calf thymus DNA (CT-DNA). The intrinsic binding constants (Kb) of complexes 1 and 2 were determined as 1.70 × 104 M–1 and 2.91 × 104 M–1, respectively, which suggests that complex 2 binds more strongly to CT-DNA than complex 1. These complexes were screened for their antimicrobial and cytotoxic activities against certain human pathogenic microorganisms and cervical cancer cells. The complexes showed moderate antibacterial and antifungal activities against certain selected microorganisms. The cytotoxic property of the complexes was tested on human cervical cancer cells, SiHa, adopting the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and specific staining techniques. The complexes affected the viability of the cells significantly and the cell death was through apoptosis as seen in the changes in the nuclear morphology and cytoplasmic features.

Chloroform Extract of Rasagenthi Mezhugu, a Siddha Formulation, as an Evidence-Based Complementary and Alternative Medicine for HPV-Positive Cervical Cancers

Rasagenthi Mezhugu (RGM) is a herbomineral formulation in the Siddha system of traditional medicine and is prescribed in the southern parts of India as a remedy for all kinds of cancers. However, scientific evidence for its therapeutic efficacy in cervical cancer is lacking, and it contains heavy metals. To overcome these limitations, RGM was extracted, and the fractions were tested on HPV-positive cervical cancer cells, ME-180 and SiHa. The extracts, free from the toxic heavy metals, affected the viability of both the cells. The chloroform fraction (cRGM) induced DNA damage and apoptosis. Mitochondria-mediated apoptosis was indicated. Though both the cells responded to the treatment, ME-180 was more responsive. Thus, this study brings up scientific evidence for the efficacy of RGM against the HPV-mediated cervical cancer cells and, if the toxic heavy metals are the limitation in its use, cRGM would be a suitable candidate as evidence-based complementary and alternative medicine for HPV-positive cervical cancers.

Cytotoxic Property of Surfactant–Cobalt(III) Complexes on a Human Breast Cancer Cell Line

The cancer chemotherapeutic potential of surfactant–cobalt(III) complexes, cis‐[Co(bpy)2(C14H29NH2)Cl](ClO4)2 · 3 H2O (1) and cis‐[Co(phen)2(C14H29NH2)Cl](ClO4)2 · 3 H2O (2) (bpy = 2,2′‐bipyridine, phen = 1,10‐phenanthroline) on MCF‐7 breast cancer cell was determined adopting MTT assay and specific staining techniques. The complexes affected the viability of the cells significantly and the cells succumbed to apoptosis as seen in the changes in the nuclear morphology and cytoplasmic features. Since the complex 2 appeared to be more potent, further assays were carried out on the complex 2. Single‐cell electrophoresis indicated DNA damage. The translocation of phosphatidyl serine and loss of mitochondrial potential was revealed by annexin V‐Cy3 staining and JC‐1 staining respectively. Western blot analysis revealed up‐regulation of pro‐apoptotic p53 and down‐regulation of anti‐apoptotic Bcl‐2 protein. Taken together, the surfactant–cobalt(III) complex 2 would be a potential candidate for further investigation for application as a chemotherapeutic for cancers in general and estrogen receptor‐positive breast cancer in particular.