Ashu Chaudhary

Synthesis, Characterization, and Evaluation of Antimicrobial and Antifertility Efficacy of Heterobimetallic Complexes of Copper (II)

Heterobimetallic complexes of the copper with remarkable antimicrobial and antifertility action have been synthesized by the conventional method by reacting CuCl2 and o-phenylenediamine in the methanolic medium forming the mononuclear complex of the type which was further treated with group 4 or 14 organometallic dichlorides (Ph2M′Cl2, Me2M′Cl2, and Cp2M′′Cl2) [M′ = Sn, Si, and M′′ = Ti, Zr] leading to formation of heterobimetallic complexes. All the synthesized complexes were characterized in the light of various physicochemical techniques like elemental analyses, conductivity measurements, molecular weight determination, electronic and infrared spectra, electronic spin resonance, X-ray, and mass spectral studies. The in vitro antibacterial activity of synthesized complexes against Escherichia coli and Staphylococcus aureus was tested to evaluate their inhibiting activities. The antifungal activities of mono- and heterobimetallic complexes were studied by screening the compounds against Fusarium oxysporum and Alternaria alternata. These complexes were then investigated to reveal their effect on the reproductive organs of male rats. The treatment has shown substantial decline in the sperm motility and density signifying the imperious antifertility activity.

Macrocyclic Assembly: A Dive into the Pecking Order and Applied Aspects of Multitalented Metallomacrocycles

To aid in knowledge of macrocyclic complexes and biomedical scientists, we are presenting here a review article with compilation of work done so far along in relation to macrocyclic ligands and their metal complexes. The metal ion chemistry of macrocyclic ligands has now become a major subdivision of coordination chemistry. This overview focuses on developments in design, synthesis, and self-assembly of metal-based architectures and ligands related to macrocyclic chemistry.

Synthesis, Spectral Characterization and Biological Study of Heterobinuclear Complexes of Cu(II) with Si(IV)

AbstractMonometallic complexes of Cu(II) of type [Cu(C12H14N4XCl)]Cl2 (where X=Cl or F) were synthesized by treating CuCl2 with the two diamines 4-chloro 1,2-phenylenediamine and 4-fluoro 1,2-phenylenediamine separately in 1:2 stiochiometric proportions. These synthesized complexes were further utilized for the preparation of heterobimetallic complexes of copper with organosilicon dichlorides (R2SiCl2) [where R=C6H5 or CH3] of the type [Cu(C36H30N4Si2XCl3)] and [Cu(C16H22N4Si2XCl3)] (where X=Cl or F). All the complexes were characterized by elemental analysis, conductance measurement, electronic spectra, IR, ESR, mass spectra and X-ray powder diffraction studies. These complexes were then evaluated for their antimicrobial efficacy with Bavistin and Streptomycin used as standards. The complexes were also tested for their plant growth regulating activity against gram plant and the results attained were quite promising. Graphical AbstractPotentially Biodynamic Heterobimetallic Complexes of Cu(II) with Si(IV)

Synthesis, Characterization, and Biological Evaluation of Unimetallic and Heterobimetallic Complexes of Bivalent Copper

We present an inclusive characterization of the unimetallic and heterobimetallic complexes of copper synthesized using CuCl2 and diamine (4-fluoro 1,2-phenylenediamine) resulting in monometallic complex which further undergoes treatment with organometallic dichlorides of group 4 and 14 in 1 : 2 molar ratio resulting in heterobimetallic complexes. These complexes thoroughly characterized using various physical, analytical, and spectroscopic techniques indicate square planar and distorted octahedral geometry for the synthesized unimetallic and heterobimetallic complexes, respectively. These complexes were evaluated for their antimicrobial efficacy against various bacterial and fungal strains while hepatoprotective activity was also examined in male albino rats.

Implications for antimicrobial, anticancer activity and molecular docking studies of N4-Tetradentate Tin macrocycles

A a noninvasive liquid biopsy, plasma cell-free DNA (cfDNA) was studied as a potentially valuable surrogate specimen for detecting tumor-specific aberrations. Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. Here, we studied cfDNA collected from subjects with advanced NSCLC by performing droplet digital PCR on serial cfDNA specimens collected from patients and healthy control. Our findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality.D to abnormal expression of integrins αvβ3 in various disease conditions, this integrin pair has been a focus as targets for drug development. Studies yield a few successful examples. Among them are various antibodies against the integrins, and most recently, Cilengitide, a RGD-based peptidomimetic.Nevertheless, most of current approaches focus on ligand-binding with goal of inhibition of integrin functions.A major draw-back of targeting ligand-binding of integrins is activation of integrin signaling by the developed agent, which largely limit the clinical success of the integrin ligand based antagonist/agonist. We report here development of a new class of therapeutically protein agent (Ref to as ProAgio) by rational protein design using a stable host protein. ProAgio is designed to target integrins αvβ3 at a novel site. ProAgio exhibits a strong in vitro activity in induction of apoptosis of integrin αvβ3 expressing cells. ProAgio induces apoptosis by recruiting and activating caspase 8 to the cytoplasmic domain of the targeted integrins. Tests with tumor xenografts show that ProAgio strongly inhibits tumor growth. Histology analyses indicate that tumor vessels are reduced, while the established vasculatures are not affected. The results confirm targeting of integrin αvβ3 as an anti-angiogenic agent. Toxicity analyses demonstrate that ProAgio is not toxic to mouse at very high doses. Our study develops an effective integrin targeting agent via a novel mechanism of action. Our approach provides a new platform for development of therapeutics by targeting integrins.Purpose: While anecdotal evidence underscores the positive impact of therapy dogs for children with cancer and their families, rigorous studies of efficacy are currently lacking, even as animal-assisted interventions (AAIs) occur daily in today’s pediatric oncology settings. This national, multi-site study is the first of its kind to rigorously measure the psychosocial effects of AAIs for this population. Specifically, researchers are interested in whether or not AAIs have positive effects on patient stress, anxiety and health-related quality of life and on parent stress and anxiety, as well as whether or not therapy dogs experience distress during AAI sessions.Introduction: Nucleophosmin1 (NPM1) gene mutation is the most frequently occurring gene mutation in Acute Myeloid Leukemia (AML) accounting for 35 to 50% of the AML patients. It encodes the nucleophosmin which is found in the cytoplasm of AML patients with variable prevalence and proven to have prognostic significance. It is involved in several activities at cellular level such as ribosomal biosynthesis, maintenance of genome stability and molecular chaperon functions. It causes inactivation of tumor suppressor gene p53. This mutation seem to identify patients that respond better to chemotherapy hence this study will help to identify patients with good prognosis. Its association with FLT3 is related to poor outcome.I 2013, the number of new cases of breast cancer in the US was 234, 580 and ~1.7 million worldwide. Despite the advances in early detection and treatment of breast cancer, about 30% of patients with early stage breast cancer have recurrent disease where resistance to therapy is common and expected. HER2 is overexpressed in 20-40% of invasive breast cancer, and 12-24% of these patients develop resistance within 6 months for the widely used therapy trastuzumab. HER2 oncogenic variant HER2 16 has been shown to promote receptor dimerization, cell invasion and also trastuzumab resistance of NIH3T3 and MCF-7 tumor cells lines. We have identified several naphthoquinones that show growth inhibition of the MCF-7 HER216 cell lines with a significantly higher potency than the present clinically used tyrosine kinase inhibitor lapatinib. These compounds also inhibit auto-phosphorylation of the Y1248 and Y1068 residues of HER2 and EGFR, respectively.Methodology: Eighty weanling female fisher (F344) rats were divided into five groups of 16 each and fed with synthetic diets containing partially-hydrogenated vegetable oil / PHVO (transfat), palmolein (saturated fatty acids) , sunflower oil (n-6 PUFA), soyabean oil (α-linoleic acid) and sunflower + fish oil(LC n-3 PUFA) for 4 months after which 8 rats from each group were administered DMBA orally, once a week, for 4 weeks and continued on same diet for 8 months, while remaining 8 rats of each group were continued on respective diets.W mammalian blood and normal tissues are usually maintained at pH around 7.4, the extracellular pH drops below 6.5 in solid cancer nests. Enzymes which function preferentially at acidic pH may be the target molecules of anti-cancer drugs. Our group have found that the inhibition of protein prenylation attenuates proliferation of cancer cells at acidic pH, suggesting that an enzyme(s) to prenylate proteins is functioning under acidic conditions. In addition to the enzyme for protein prenylation, there may be other enzymes functioning under acidic conditions. To find such enzymes, the expression of 24,000 genes was examined using a DNA array chip in mesothelioma cells, and the expression of approximately 700 genes was elevated at acidic pH. The elevated expression of these genes was found in other cancer cells grown under acidic conditions and in human specimens from cancer patients. These results suggest that mammalian cells have many enzymes which function preferentially in acidic cancer nests, and that drugs inhibiting these enzymes could be potent candidates for anticancer chemotherapeutics with less side-effect, especially on immune systems in blood and normal tissues, because acidosisdependent drugs are expected to be less effective in tissues whose pH is alkaline. In fact, inhibitors of protein prenylation had little effect on proliferation and cytokine production of immune cells at alkaline pH. The screening under acidic conditions may be a useful way to find new anti-cancer drugs which are effective in acidic cancer nests.A R1R2NOR3 are able to undergo homolysis upon chemical activation to release a stable nitroxide R1R2NO•, which can be used for DNP-MRI, and a transient alkyl radical R3•, which can be used for killing tumor cells. By combining diagnostic and therapeutic activities into a single low-molecular weight molecule, alkoxyamines are new theranostic tools. We have developed this concept recently, and proved that they are reliable and controllable sources of in-situ generated radicals able to exhibit interesting biological and imaging properties.Multiple spinal tumors are known to occur in association with phacomatosis like neurofibromatosis. Rarely, sporadic occurrences have been described in the absence of a clear underlying pathogenesis. The majority of intradural extramedullary spinal tumors are meningiomas or nerve sheath tumors like schwannoma and neurofibroma. Ependymomas, which are the most common intramedullary spinal tumors in adults, can also occur in the extramedullary intradural space and impose a diagnostic challenge. Only a few such cases have been described in the literature. We report the first sporadic occurrence of an intradural extramedullary ependymoma synchronously presenting with a different neoplasm, a schwannoma. A 43-year-old woman presented to the authors’ institution with lumbosacral pain and neurological deficits lasting a decade. On magnetic resonance imaging, she was found to have two stable, contrast-enhancing intradural extramedullary spinal lesions in the L2-3 and L4-5 vertebral areas. She subsequently underwent L2-L5 laminectomy with total resection of the former lesion and subtotal resection of the later lesion. Histological and immunohistochemical analysis revealed two distinct tumors: a cellular ependymoma and a schwannoma at the two respective locations. Ependymomas are low grade, slowly growing tumors that mimic other, benign tumors clinically as well as radiologically. However, the management of these tumors differs since ependymomas have a potential for recurrence and metastasis. The underlying etiology and pathogenesis of these tumors is not clearly established. However, an association with an underlying phacomatosis needs to be considered. Our purpose is to create awareness that an intradural extramedullary ependymoma can coexist with other spinal tumors and should be included in the differential diagnosis of a multifocal spinal lesion presentation. Owing to difficulties in differentiating these closely mimicking spinal tumors clinically and radiologically, early identification with surgical resection, when possible, might be a recommended strategyA monoclonal antibody (Mab) designated as GHR106 was generated against the extracellular domain (N1-29 synthetic peptide) of human gonadotropin releasing hormone (GnRH) receptor. It is a first-in-class GnRH analog and can serve as a drug candidate for potential applications in the treatment of human cancers and/or fertility regulations. Both Mabs in murine (mGHR106) or humanized (hGHR106) forms were shown to have comparable specificity and affinity to intact GnRH receptor on cancer cells or to N1-29 synthetic peptides from humans and monkeys. Similar to decapeptide GnRH analogs, both Mabs were shown to induce apoptosis to cultured cancer cells of various tissue origins, including those from the ovary, breast, prostate, and lung. However, both Mabs were also found to induce complement-dependent cytotoxicity (CDC) reaction for lysis of cancer cells, an immune property which is not shared by peptide analogs of GnRH. By using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), both GHR106 Mabs and the GnRH decapeptide antagonist, Antide, were shown to be bioequivalent in terms of their respective effects on genes involved in the proliferation and apoptosis of cancer cells. In addition, GHR106 Mabs have a much longer circulating half-life than GnRH peptide analogs (days versus hours). Based on the results of these studies, it can be concluded that both mGHR106 and hGHR106 are bioequivalent to the GnRH decapeptide antagonist, Antide, in many biological and functional properties. Therefore, hGHR106 can serve as a long-acting alternative to the current decapeptide GnRH antagonists for therapeutic treatments in the immunotherapy of human cancers, including those of gynecologic origin.