307 research outputs found
Copper complexes as prospective anticancer agents: <i>in vitro</i> and <i>in vivo</i> evaluation, selective targeting of cancer cells by DNA damage and S phase arrest
No full textThe thiosemicarbazone-based copper(i) complexes causing S phase arrest and apoptosis involving the mitochondrial controlled pathway has been investigated.</p
Green synthesis of a redox-active riboflavin-integrated Ni-MOF and its versatile electrocatalytic applications towards oxygen evolution and reduction, and HMF oxidation reactions
No full textThe post-synthetic modification (PSM) of metal-organic frameworks (MOFs) with redox-active molecules under mild conditions is a highly challenging approach to modify the inherent properties of MOFs without altering their crystallinity and other characteristics. Here, we prepared a single crystal Ni-MOF with a two-dimensional rod-like morphology. Furthermore, we utilized the PSM technique to incorporate redox-active riboflavin (Rbf) in the Ni-MOF using a green and facile mechanochemical method under solvent-free conditions. The Rbf-doped Ni-MOF (Rbf-Ni-MOF) showed a 4-fold increase in conductivity compared to the pristine Ni-MOF. We employed the Rbf-Ni-MOF as a multifunctional electrocatalyst towards the oxygen evolution reaction (OER), oxygen reduction reaction (ORR) and oxidation of 5-hydroxymethylfurfural (HMF). As an OER electrocatalyst, the Rbf-Ni-MOF delivered a high current density of 580 mA cm−2, which is around 26-fold greater than those of Rbf and the pristine Ni-MOF. The prep..
Zinc(II) complexes of indole thiosemicarbazones: DNA/protein binding, molecular docking and in vitro cytotoxicity studies
No full textFour Zn(II) complexes (1–4) featuring indole thiosemicarbazones were synthesized and well-characterized by elemental analyses and various spectroscopic (UV–Vis, FT-IR, 1H NMR, 13C NMR and mass) techniques. The single crystal X-ray crystallographic study revealed a tetrahedral geometry for complexes 1 and 3. The interactions of the Zn(II) complexes 1–4 with calf thymus DNA (CT DNA) were examined by UV–Vis spectroscopy and viscosity measurements, which implied that the complexes bound to CT DNA via intercalation, and complex 4 showed a higher binding affinity than the other complexes. The protein binding interaction of the complexes was monitored by fluorescence and absorption techniques, which showed that the complexes could bind effectively with bovine serum albumin (BSA) and the type of quenching mechanism was found to be static. Synchronous fluorescence experiments showed the changes in the conformations of the protein micro regions. Molecular docking studies were performed in order to get a better picture of the binding of the complexes with the molecular targets DNA hexamer and BSA. The in vitro cytotoxicity of the complexes against two human cancer (A549 and MCF7) cell lines, two human non-tumorigenic (MCF-10A and HEK-293) cell lines and one non-cancerous mouse fibroblasts (L929) cell line was evaluated using an MTT assay. Complex 4, which has an N-terminal cyclohexyl group, showed moderate activity [IC50 = 37.9 (A549) and 60.3 μM (MCF7)] that was comparable with the familiar anticancer drug cisplatin. Also, fortunately, the activity of complex 4 was found to be specific to cancer cells. The apoptosis cell death mechanism for complex 4 was assessed by the Hoechst staining method.No Full Tex
Copper(I) complexes of acylthiourea ligands: structural insights and cytotoxic potential
No full textThe reaction of substituted acylthiourea derivatives (L1–L4) with [(PPh3)2Cu(μ-Cl)2Cu(PPh3)] in a proper stoichiometric proportion gave the complexes (1–4) in good yields. The structures of the compounds (ligands and complexes) were advocated through spectroscopic analyses and x-ray diffraction (XRD) studies; the latter confirmed their molecular structures. The complexes (1–4) were assessed for their cytotoxic potential through MTT assay against A549, T24, and HepG2 cancer cells, and their toxicity was evaluated using Vero and MCF-10a normal cells. The complexes (1–4) displayed better cytotoxic action toward HepG2 cancer cells than cisplatin. Complexes 3 and 4 significantly destroyed A549 cancer cells with the IC50 values of 16.25 and 4.90 μM, respectively, which were lower than that of cisplatin (IC50 = 17.73 μM). Furthermore, the higher IC50 values in normal cells showed that the complexes were less hazardous to the normal cells except complex 3. The biocompatibility study showed that the complexes had minimal impact on normal human dermal fibroblast (NHDF) cells. The mode of cell death of complexes 3 and 4 against cancer cells was evaluated using staining assays. Both compounds demonstrated a significant reduction in live cells, an increase in early apoptotic cells, and pronounced proapoptotic effects, as evidenced by fragmented nuclei. Flow cytometry revealed a distinctive subpopulation in the subG0 phase, highlighting the compounds' ability to induce apoptosis and inhibit cell cycle progression.No Full Tex
Synthesis, characterization and cytotoxic activity of novel copper(II) complexes with aroylhydrazone derivatives of 2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde
No full textThree new 2-oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde terminal substituted aroylhydrazone ligands (2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde(2′-hydroxybenzoyl)hydrazine, H2L1, 1, 2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde(2′-hydroxybenzoyl)hydrazine, H2L2, 2, 2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde(2′-hydroxybenzoyl)hydrazine, H2L3, 3) and the corresponding novel copper(II) complexes [Cu(L)(CH3OH)(NO3)](L = HL1 (4), HL2 (5), HL3 (6-6+), have been synthesized to compare their coordination behaviour and biological activity with respect to the presence of an OH group in different positions of the phenyl ring in the hydrazone moieties. The new ligands and their copper complexes were characterized by elemental analysis and spectroscopic techniques. The molecular structures of the new complexes 4 and 6-6+ were determined by single crystal X-ray diffraction. The interactions of the free ligands and their copper complexes with calf thymus DNA were tested by absorption measurements and ethidium bromide competitive studies which revealed that all compounds may interact with calf thymus DNA through intercalation. Furthermore, a comparative analysis of the cytotoxic effect of the compounds on a panel of human cancer cell lines showed that the copper complexes exhibited in vitro antitumor activity significantly higher than that of the free ligands and also of cisplatin
Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2
No full textMetal complexes have numerous applications in the current era, particularly in the field of pharmaceutical chemistry and catalysis. A novel synthetic approach for the same is always a beneficial addition to the literature. Henceforth, for the first time, we report the formation of three new Pd(II) complexes through the Michael addition pathway. Three chromone-based thiosemicarbazone ligands (SVSL1-SVSL3) and Pd(II) complexes (1-3) were synthesized and characterized by analytical and spectroscopic tools. The Michael addition pathway for the formation of complexes was confirmed by spectroscopic studies. Distorted square planar structure of complex 2 was confirmed by single-crystal X-ray diffraction. Complexes 1-3 were subjected to DNA- and BSA-binding studies. The complex with cyclohexyl substituent on the terminal N of thiosemicarbazone (3) showed the highest binding efficacy toward these biomolecules, which was further understood through molecular docking studies. The anticancer potential of these complexes was studied preliminarily by using MTT assay in cancer and normal cell lines along with the benchmark drugs (cisplatin, carboplatin, and gemcitabine). It was found that complex 3 was highly toxic toward MDA-MB-231 and AsPC-1 cancer cells with IC50 values of 0.5 and 0.9 μM, respectively, and was more efficient than the standard drugs. The programmed cell death mechanism of the complexes in MDA-MB-231 cancer cells was confirmed. Furthermore, the complexes induced apoptosis via ROS-mediated mitochondrial signaling pathway. Conveniently, all the complexes showed less toxicity (≥50 μM) against MCF-10a normal cell line. Molecular docking studies were performed with VEGFR2, EGFR, and SARS-CoV-2 main protease to illustrate the binding efficiency of the complexes with these receptors. To our surprise, binding potential of the complexes with SARS-CoV-2 main protease was higher than that with chloroquine and hydroxychloroquine.No Full Tex
Study to Assess Physical Health Status of Children at Selected Orphanage in Salem, Chennai – India
No full textOrphanages are a vulnerable group in any socio-economic setting simply because they are deprived of one or both of their primary care givers. The level of vulnerability they face however increases significantly with the level of poverty. In India below 18’s population is 42,06,78,000 among them 2,57,00,000 are orphan children. That constitute a major part of the below 18’s population (UNICEF, 2005). Orphans are a group of underprivileged population in society. The evidence from the pediatric and child psychiatry literature makes clear that orphanages are neither an effective nor a humane mode of assistance to infants and families. Orphans are some of the most underprivileged children in the world. With few exceptions, children without parents are deprived of many of the basic rights such as food, shelter, education, and a family environment. Orphanage children are deprived of their primary care givers thus more prone to physical health problems
Effect of coordination mode of thiosemicarbazone on the biological activities of its Ru(II)-benzene complexes: Biomolecular interactions and anticancer activity via ROS-mediated mitochondrial apoptosis
No full textRu(II)-benzene complexes (P1 and P2) were synthesized using a thiosemicarbazone ligand (L1) in two different coordination modes, monodentate S and bidentate N,S, through carefully adjusted reaction conditions. Comprehensive characterization of the complexes was achieved through single crystal X-ray diffraction, revealing a piano-stool geometry around the Ru(II) ion. To evaluate the binding capabilities of the complexes towards CT DNA and BSA, UV–Vis and/or hydrodynamic methods were utilized. Docking studies further validated the intercalative binding mode with DNA, in agreement with the experimental findings, and identified specific BSA amino acids involved in the binding interactions. Based on the results of binding studies, cytotoxicity of the ligand and complexes was appraised in various cancer and normal cell lines alongside the commercial pharmaceutics. Complexes P1 and P2 displayed a promising activity against MDA-MB-231 [IC50 = 5.11 (P1) and 3.48 μM (P2)] and PANC-1 [IC50 = 7.20 (P1) and 4.85 μM (P2)] cancer cells; with the bidentate system (P2) exhibiting a higher activity than its monodentate congener P1, although both of them showed superior activity than the reference drugs. Various bioassays including Western blot analysis revealed the mode of cell death to be apoptosis, which was further concluded to be via the ROS-mediated mitochondrial signaling pathway
Influence of Indole-N Substitution of Thiosemicarbazones in Cationic Ru(II)(η6-Benzene) Complexes on Their Anticancer Activity
No full textIndole thiosemicarbazones (TSCs) and their complexes are known to possess various biological activities. The variation in anticancer activity with different indole-N substituents of TSCs in the RuII-benzene complexes (C1-C7) was studied. The complexes were adequately characterized using analytical and spectroscopic techniques. The single crystal X-ray diffraction (XRD) technique confirmed the piano-stool structure of the complexes (C4 and C7). The theoretical findings on the structure of complexes supported the experimental results. The complexes (C1-C7) exhibited good biomolecular interactions with DNA/protein and significant anticancer potential against MB-MDA-231 and MCF-7 cancer cells. Also, the complexes were least toxic to normal human cells, suggesting the selectivity of the complexes. The benzyl substituent at indole-N of the TSC ligands seemed to improve the cytotoxic profile of their complexes compared to the allyl one. Among the benzyl scaffolds, the para-substituted [methyl (C5) and chloro (C6)] ones elevated the anticancer activity compared to the meta-substituted compounds (C4 and C7). Hoechst and AO-EB staining assisted the visualization of the apoptotic changes induced by active complexes C2 and C6 in MB-MDA-231 cells. Further, flow cytometric analysis authenticated the cell cycle arrest in the sub-G0/G1 phase. Western blotting studies confirmed the apoptotic mode of cell death by quantifying the proapoptotic and antiapoptotic proteins.No Full Tex
Ferulic acid dimer as a non-opioid therapeutic for acute pain
No full textAlaini Priebe,1,* Megan Hunke,1,* Raquel Tonello,2 Yogesh Sonawane,3 Temugin Berta,2 Amarnath Natarajan,3 Nattamai Bhuvanesh,4 Mahesh Pattabiraman,5 Surabhi Chandra1 1Department of Biology, University of Nebraska-Kearney, Kearney, NE, USA; 2Department of Anesthesiology, University of Cincinnati, Cincinnati, OH, USA; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Chemistry, Texas A&M University, TX, USA; 5Department of Chemistry, University of Nebraska-Kearney, Kearney, NE, USA *These authors contributed equally to this work Purpose: Search for alternate pain medications has gained more importance in the past few years due to adverse effects associated with currently prescribed drugs including nervous system dysfunction with opioids, gastrointestinal discomfort with nonsteroidal anti-inflammatory drugs, and cardiovascular anomalies with cyclooxygenase-2 (COX-2) inhibitors. Phytomedicine has been explored for the treatment of pain, as these have been used for generations in regional communities and tend to lack major side effects in general. One such phytomedicine, incarvillateine (INCA), derived from the Chinese herb Incarvillea sinensis has its primary antinociceptive action through the adenosine receptor, a novel pain target. We hypothesized that derivatives of cinnamic acid dimers, which are structurally similar to INCA, would show potent antinociceptive action and that their effect would be mediated through adenosine receptor action. Materials and methods: Dimers of cinnamic acid (INCA analogs) were synthesized using cavitand-mediated photodimerization (CMP) method, which utilizes a macromolecule (γ-cyclodextrin) to control excited state reactivity of photoactive compounds. Acute pain response was assessed by using formalin-induced licking behavior in hind paw of mice, and neurologic function was monitored through locomotor activity, mechanical hyperalgesia, and thermal sensitivity upon administration of test compound. For mechanistic studies, binding to adenosine receptor was determined by using computer modeling. Results: Ferulic acid dimer (FAD), which has the same chemical functionalities on the aromatic ring as INCA, showed significant suppression of formalin-induced acute pain. Antinociceptive effect was observed primarily in the inflammatory phase, and no apparent behavioral changes related to the nervous system were noticeable. Inhibition of opioid receptor did not reverse antinociceptive response, and modeling data suggest adenosine 3 receptor binding. Conclusion: FAD (INCA analog) shows potent nonopioid antinociceptive action mediated predominantly through A3AR – adenosine 3 receptor action. Further characterization and selection of such INCA analogs will help us generate a new class of antinociceptives with precise chemical modifications by using CMP methodology. Keywords: adenosine, incarvillateine, cinnamic acid, formalin, antinociceptiv
- …
