29 results on '"Anjani K. Tiwari"'
Search Results
2. Benzoxazolone‐arylpiperazinyl scaffold‐based PET ligand for 5‐HT 7 : Synthesis and biological evaluation
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Neelam Kumari, Anupriya Adhikari, Deepika Singh, Sunita Bhagat, Himanshu Ojha, and Anjani K. Tiwari
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Drug Discovery - Published
- 2022
3. Mapping of Translocator Protein (18 kDa) in Peripheral Sterile Inflammatory Disease and Cancer through PET Imaging
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Ming-Rong Zhang, Anupriya Adhikari, Anjani K. Tiwari, Bhawana Adhikari, Kamalesh Singh Mahar, Manish Adhikari, and Priya Singh
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Cell ,Pharmaceutical Science ,Inflammation ,02 engineering and technology ,Disease ,Ligands ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Receptors, GABA ,Downregulation and upregulation ,Neoplasms ,Drug Discovery ,Translocator protein ,Animals ,Humans ,Medicine ,biology ,business.industry ,Cancer ,021001 nanoscience & nanotechnology ,medicine.disease ,Molecular Imaging ,Up-Regulation ,Biomarker (cell) ,Disease Models, Animal ,medicine.anatomical_structure ,Positron-Emission Tomography ,Cancer research ,biology.protein ,Molecular Medicine ,medicine.symptom ,0210 nano-technology ,business ,Biomarkers - Abstract
Positron emission tomography (PET) imaging of the translocator 18 kDa protein (TSPO) with radioligands has become an effective means of research in peripheral inflammatory conditions that occur in many diseases and cancers. The peripheral sterile inflammatory diseases (PSIDs) are associated with a diverse group of disorders that comprises numerous enduring insults including the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system. TSPO has recently been introduced as a potential biomarker for peripheral sterile inflammatory diseases (PSIDs). The major critical issue related to PSIDs is its timely characterization and localization of inflammatory foci for proper therapy of patients. As an alternative to metabolic imaging, protein imaging expressed on immune cells after activation is of great importance. The five transmembrane domain translocator protein-18 kDa (TSPO) is upregulated on the mitochondrial cell surface of macrophages during inflammation, serving as a potential ligand for PET tracers. Additionally, the overexpressed TSPO protein has been positively correlated with various tumor malignancies. In view of the association of escalated TSPO expression in both disease conditions, it is an immensely important biomarker for PET imaging in oncology and PSIDs. In this review, we summarize the most outstanding advances on TSPO-targeted PSIDs and cancer in the development of TSPO ligands as a potential diagnostic tool, specifically discussing the last five years.
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- 2021
4. Receptor mapping using methoxy phenyl piperazine derivative: Preclinical PET imaging
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Meganathan Thirumal, Anupama Datta, Anjani K. Tiwari, K. Ganesh Kadiyala, and Garima Mann
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Biodistribution ,Pharmacology ,Ligands ,Receptors, Metabotropic Glutamate ,Biochemistry ,Piperazines ,chemistry.chemical_compound ,Mice ,Drug Discovery ,Animals ,Humans ,Tissue Distribution ,Receptor ,Molecular Biology ,Mice, Inbred BALB C ,Molecular Structure ,Organic Chemistry ,Brain ,Ligand (biochemistry) ,Haemolysis ,Healthy Volunteers ,Rats ,Piperazine ,chemistry ,Metabotropic glutamate receptor ,Positron-Emission Tomography ,Metabotropic glutamate receptor 1 ,Specific activity - Abstract
This study aimed at assessing 2-methoxyphenyl piperazine derivative for its binding specificity and suitability in mapping metabotropic glutamate receptor subtype 1, which is implicated in several neuropsychiatric disorders. N-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)-N-methylpyridin-2-amine was synthesised and evaluated for brain imaging subsequent to radiolabelling with [11C] radioisotope via methylation process in 98.9% purity and 52 ± 6% yield (decay corrected). The specific activity was in the range of 72–93 GBq/µmol. The haemolysis of blood was 2–5% for initial 4 hr and remained The PET as well as biodistribution studies also showed high activity in the brain with a direct correlation between receptor abundance distribution pattern and tracer activity. The biodistribution analyses revealed initial high brain uptake (4.18 ± 0.48). The highest uptake was found in cerebellum (SUV 4.7 ± 0.2), followed by thalamus (SUV 3.5 ± 0.1), and striatum (SUV 3 ± 0.1). In contrast, pons had negligible tracer activity. The high uptake observed in all the regions with known mGluR1 activity indicates suitability of the ligand for mGluR1 imaging.
- Published
- 2021
5. Chalcone Based Homodimeric PET Agent, 11C-(Chal)2DEA-Me, for Beta Amyloid Imaging: Synthesis and Bioevaluation
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Anjani K. Tiwari, Ankur Kaul, Anupama Datta, Ajai K. Singh, Nidhi Chadha, and Kanchan Chauhan
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0301 basic medicine ,Chalcone ,Stereochemistry ,Amyloidosis ,Pharmaceutical Science ,Plasma protein binding ,Ligand (biochemistry) ,medicine.disease ,Fibril ,Amyloid Beta 42 ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Monomer ,chemistry ,Drug Discovery ,medicine ,Molecular Medicine ,Specific activity ,030217 neurology & neurosurgery - Abstract
Homodimeric chalcone based 11C-PET radiotracer, 11C-(Chal)2DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aβ) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aβ fibrils. The bivalent ligand 11C-(Chal)2DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11C-Chal-Me, and classical Aβ agents. The radiolabeling yield with carbon-11 was 40–55% (decay corrected) with specific activity of 65–90 GBq/μmol. A significant (p 93% intact tracer at 30 min po...
- Published
- 2018
6. Synthesis and evaluation of technetium-99m labelled 1-(2-methoxyphenyl)piperazine derivative for single photon emission computed tomography imaging for targeting 5-HT1A
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Sunita Bhagat, Krishna Srivastava, Raunak Varshney, Neelam Kumari, Anil K. Mishra, Vinay Singh, Anjani K. Tiwari, and Ankur Kaul
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Biodistribution ,Kidney ,medicine.diagnostic_test ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Pharmacology ,Single-photon emission computed tomography ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,medicine.anatomical_structure ,Pharmacokinetics ,Spect imaging ,Drug Discovery ,medicine ,Distribution (pharmacology) ,Receptor ,Molecular Biology ,Technetium-99m - Abstract
Quantitative changes in expression level of 5HT1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT1A imaging. 99mTc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99mTc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species.
- Published
- 2021
7. Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential anticancer agent: Synthesis and evaluation
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Neelam Kumari, Abha Shukla, Nitin Kumar, Anjani K. Tiwari, Anil K. Mishra, Manish Adhikari, Anupriya Adhikari, and Anupama Datta
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Biodistribution ,Stereochemistry ,DNA damage ,Clinical Biochemistry ,Mice, Nude ,Pharmaceutical Science ,Antineoplastic Agents ,Cyclams ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cyclen ,Heterocyclic Compounds ,Cell Line, Tumor ,Spect imaging ,Drug Discovery ,Organometallic Compounds ,Animals ,Humans ,DNA Cleavage ,Molecular Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Organic Chemistry ,Tryptophan ,Neoplasms, Experimental ,0104 chemical sciences ,Comet assay ,Zinc ,HEK293 Cells ,chemistry ,Phosphodiester bond ,Molecular Medicine ,Drug Screening Assays, Antitumor ,DNA - Abstract
With the rising incidences of cancer cases, the quest for new metal based anticancer drugs has led to extensive research in cancer biology. Zinc complexes of amino acid residue side chains are well recognized for hydrolysis of phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II) complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp)2 has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen-(Trp)2 was synthesized in ∼70% yield and its DNA binding potential was evaluated through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The decrease in intensity of the positive and negative bands of CT-DNA at 278nm and 240nm, respectively demonstrated an effective unwinding of the DNA helix with loss of helicity. The complex was identified as an antiproliferative agent against U-87MG cells with 5 fold increase in apoptosis with respect to control (2h post incubation, IC50 25µM). Electrophoresis and comet assay studies exhibited an increase in DNA breakage after treatment with complex while caspase-3/β-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87 MG cells after triggering DNA damage. In vivo tumor specificity of the developed ligand was validated after radiocomplexation with 99mTc (>98% radiochemical yield and specific activity of 2.56GBq/µmol). Avid tumor/muscle ratio of >6 was depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model nude mice.
- Published
- 2017
8. Modified benzoxazolone (ABO-AA) based single photon emission computed tomography (SPECT) probes for 18 kDa translocator protein
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Pooja Srivastava, Pravir Kumar, Dipti Kakkar, and Anjani K. Tiwari
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Lipopolysaccharides ,Lung Diseases ,Male ,Biodistribution ,Stereochemistry ,Protein Data Bank (RCSB PDB) ,Single-photon emission computed tomography ,Scintigraphy ,03 medical and health sciences ,chemistry.chemical_compound ,Radioligand Assay ,0302 clinical medicine ,Receptors, GABA ,Drug Discovery ,medicine ,Translocator protein ,Animals ,Humans ,Fluorescent Dyes ,chemistry.chemical_classification ,Inflammation ,Tomography, Emission-Computed, Single-Photon ,Benzoxazoles ,Mice, Inbred BALB C ,medicine.diagnostic_test ,biology ,Chemistry ,Technetium ,A549 Cells ,030220 oncology & carcinogenesis ,Lipophilicity ,biology.protein ,Propionate ,Rabbits ,030217 neurology & neurosurgery ,Acetamide - Abstract
Acetamidobenzoxazolone (ABO) has been modified to ABO-AA, 2-(2-(5-bromo/chloro benzoxazolone)acetamide)-3-(1H-indol-3-yl)propionate to improve pharmacokinetics and lipophilicity (log p = 2.04). The final compound was synthesized in better yield and in fewer steps than previously reported MBIP-Br (70% vs. 62%). Computational docking confirmed binding of MBIP-Cl with translocator protein (TSPO) as well as with mutant TSPO (-8.99 for PDB: 4RYQ and -9.30 for PDB: 4UC1, respectively). Ex-vivo biodistribution and scintigraphy showed that 99m Tc-MBIP-Cl is better than 99m Tc-MBIP-Br in terms of uptake in TSPO-rich organs and release kinetics 0-120 min postinjection. At 15 min, uptake was 2.75-fold (12.91%ID/g vs. 4.69%ID/g) in lung and seven-fold (5.16%ID/g vs. 0.72%ID/g) in heart for 99m Tc-MBIP-Cl compared to that of 99m Tc-MBIP-Br which gives warrant to utilize this single photon emission computed tomography agent in higher animals.
- Published
- 2019
9. Synthesis and biological evaluation of modified laminin peptide (N2S2-KDP) with enhanced affinity for neuronal growth and targeted molecular imaging (SPECT)
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Roger Strömberg, Aruna Kaushik, Puja Panwar Hazari, Ankur Kaul, Anjani K. Tiwari, Sweta Singh, Meenakshi Saklani, Raunak Varshney, Anil K. Mishra, and Rashi Mathur
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chemistry.chemical_classification ,Neurite ,biology ,010405 organic chemistry ,Organic Chemistry ,Peptide ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Amino acid ,Cell biology ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,chemistry ,Laminin ,Cell culture ,Drug Discovery ,Peptide synthesis ,biology.protein ,Isoleucine ,Receptor ,Molecular Biology - Abstract
An analog of γ1 laminin (RDIAEIIKDI) decapeptide has been used to augment neuronal survival and regeneration after injuries, during aging and other CNS disorder. As a prime synthetic peptide, KDI, is responsible for the neurite outgrowth of human embryonic neurons. In this study, we have designed, modified a KDI derivative and synthesized by replacing isoleucine (I) with Pro (P) amino acid at C-terminal to enhance its potency towards neurite growth. -Cys-Gly-Cys (-CGC) N2S2 motif was also incorporated in the present design for peptide radiolabeling. The modified peptide showed a better binding with the desired 3T1M receptor for neurite growth. The peptide was synthesized using solid phase peptide synthesis and Fmoc-strategy with more than 80% yield. The receptor binding studies of 99mTc-N2S2-KDP in Neuro2A cell lines showed Kd value in 31 nM range and the complex showed appreciable brain uptake in mice. The results on human SH-SY5Y indicate that the unlabeled N2S2-KDP may perhaps be useful for neurite growth in neurodegenerative disorder.
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- 2021
10. Design and synthesis of calcium responsive magnetic resonance imaging agent: Its relaxation and luminescence studies
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Anil K. Mishra, Jyoti Tanwar, Meganathan Thirumal, Anupama Datta, K. Ganesh Kadiyala, Anjani K. Tiwari, Sunil Pal, S. Senthil Kumaran, and Kanchan Chauhan
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Pharmacology ,Luminescence ,Molecular Structure ,Chemistry ,MRI contrast agent ,Gadolinium ,Metal ions in aqueous solution ,Organic Chemistry ,Relaxation (NMR) ,Contrast Media ,chemistry.chemical_element ,General Medicine ,Calcium ,Inner sphere electron transfer ,Magnetic Resonance Imaging ,Nuclear magnetic resonance ,Coordination Complexes ,Drug Design ,Luminescent Measurements ,Drug Discovery ,Water binding - Abstract
Calcium concentration modulation both inside and outside cell is of considerable interest for nervous system function in normal and pathological conditions. MRI has potential for very high spatial resolution at molecular/cellular level. Design, synthesis and evaluation of Gd-DO3A-AME-NPHE, a calcium responsive MRI contrast agent is presented. The probe is comprised of a Gd(3+)-DO3A core coupled to iminoacetate coordinating groups for calcium induced relaxivity switching. In the absence of Ca(2+) ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is restricted with longitudinal relaxivity, r1 = 4.37 mM(-1) s(-1) at 4.7 T. However, addition of Ca(2+) triggers a marked enhancement in r1 = 6.99 mM(-1) s(-1) at 4.7 T (60% increase). The construct is highly selective for Ca(2+) over competitive metal ions at extracellular concentration. The r1 is modulated by changes in the hydration number (0.2 to 1.05), which was confirmed by luminescence emission lifetimes of the analogous Eu(3+) complex. T1 phantom images establish the capability of complex of visualizing changes in [Ca(2+)] by MRI.
- Published
- 2014
11. Design, Synthesis, and Biological Evaluation of Catecholamine Vehicle for Studying Dopaminergic System
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Krishna Chuttani, Vikas Kumar, Swati Aggarwal, Ramendra Pratap, Anil K. Mishra, Pooja Singh, and Anjani K. Tiwari
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Models, Molecular ,Biodistribution ,Protein Data Bank (RCSB PDB) ,Serum albumin ,Biochemistry ,Catecholamines ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Tissue Distribution ,Radionuclide Imaging ,IC50 ,Edetic Acid ,Serum Albumin ,Pharmacology ,Quenching (fluorescence) ,biology ,Chemistry ,Organic Chemistry ,Brain ,Technetium ,Organotechnetium Compounds ,Ligand (biochemistry) ,Human serum albumin ,Acetylcholinesterase ,biology.protein ,Molecular Medicine ,Rabbits ,Protein Binding ,medicine.drug - Abstract
Catecholamine mimetic EDTA-bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand-human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex = 350 nm found to be 5.847 × 10(4) m(-1) shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 μm for MAO-B inhibition. Finally, EDTA-bis(tyramide) labeled with (99m) Tc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for (99m) Tc-EDTA-bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body.
- Published
- 2013
12. Investigation for the Interaction of Tyramine-Based Anthraquinone Analogue with Human Serum Albumin by Optical Spectroscopic Technique
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Gurmeet Singh, Swati Aggarwal, Nidhi Chadha, Anjani K. Tiwari, Pooja Srivastava, Anil K. Mishra, and Vikas Kumar
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Pharmacology ,Anthraquinone Analogue ,Molecular model ,Stereochemistry ,Chemistry ,Organic Chemistry ,Human serum albumin ,Biochemistry ,Binding constant ,Fluorescence ,Anthraquinone ,Fluorescence spectroscopy ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Molecular Medicine ,HOMO/LUMO ,medicine.drug - Abstract
A newly synthesized anthraquinone derivative 'N-(2-methylanthraquinone)-4-(2-aminoethyl) phenol' (Tyan) were characterized as a fluorophore from photophysical analysis by measuring the UV-Vis absorptive (λ(ex) = 325 nm) and fluorescence emitive (λ(em) = 660 nm) values. Density functional theory additionally supported the spectroscopic data by modulation of highest occupied molecular orbital rather than lowest unoccupied molecular orbital due to the affect of tyramine moiety present in Tyan. The pharmacological importance of Tyan was evaluated by molecular docking with human serum albumin. The molecular docking of the Tyan was performed with the crystal structure of human serum albumin (PDB entry 1E78), which shows binding in all the three domains of human serum albumin corresponding to -7.74 as the GScore. Moreover, the interactions of human serum albumin with Tyan were assessed employing fluorescence spectroscopy under simulative physiological conditions, and the binding constant for the interaction at 25 °C was found to be 0.6 × 10(3)/M.
- Published
- 2012
13. Modified benzoxazolone derivative as 18-kDa TSPO ligand
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Nidhi Chadha, Sunita Bhagat, Lokesh C. Mishra, Neelam Kumari, Pooja Srivastava, Anjani K. Tiwari, and Anil Mishra
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0301 basic medicine ,Plasma protein binding ,Ligands ,Biochemistry ,Molecular Docking Simulation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Suzuki reaction ,Receptors, GABA ,Drug Discovery ,Translocator protein ,Animals ,Pharmacology ,Benzoxazoles ,biology ,Chemistry ,Ligand ,Organic Chemistry ,In vitro binding ,030104 developmental biology ,Docking (molecular) ,biology.protein ,Molecular Medicine ,030217 neurology & neurosurgery ,Protein Binding - Abstract
We have synthesized six new congeners of acetamidobenzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8 ± 1.2 nm) for TSPO was found for N-methyl-2-(5-(naphthalen-1-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-phenylacetamide, (NBMP). NBMP was synthesised by Suzuki coupling reaction between 2-(5-bromo-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-phenylacetamide and napthalene-1-boronic acid. Computational docking and simulation studies showed not much impact of intersubject variability on binding which is one of the major drawbacks of several TSPO ligands. These findings suggested that NBMP may become a promising marker for visualization of neuroinflammation via TSPO targeting.
- Published
- 2016
14. In Silico Designing and Analysis of Inhibitors against Target Protein Identified through Host-Pathogen Protein Interactions in Malaria
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Anjani K. Tiwari, Monika Samant, Nidhi Chadha, and Yasha Hasija
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0301 basic medicine ,Article Subject ,In silico ,Computational biology ,Pharmacology ,01 natural sciences ,Biochemistry ,Protein–protein interaction ,03 medical and health sciences ,Interaction network ,Drug Discovery ,medicine ,Pathogen ,biology ,lcsh:RM1-950 ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Docking (molecular) ,Molecular Medicine ,Target protein ,Malaria ,Research Article - Abstract
Malaria, a life-threatening blood disease, has been a major concern in the field of healthcare. One of the severe forms of malaria is caused by the parasite Plasmodium falciparum which is initiated through protein interactions of pathogen with the host proteins. It is essential to analyse the protein-protein interactions among the host and pathogen for better understanding of the process and characterizing specific molecular mechanisms involved in pathogen persistence and survival. In this study, a complete protein-protein interaction network of human host and Plasmodium falciparum has been generated by integration of the experimental data and computationally predicting interactions using the interolog method. The interacting proteins were filtered according to their biological significance and functional roles. α-tubulin was identified as a potential protein target and inhibitors were designed against it by modification of amiprophos methyl. Docking and binding affinity analysis showed two modified inhibitors exhibiting better docking scores of −10.5 kcal/mol and −10.43 kcal/mol and an improved binding affinity of −83.80 kJ/mol and −98.16 kJ/mol with the target. These inhibitors can further be tested and validated in vivo for their properties as an antimalarial drug.
- Published
- 2016
15. Design, Synthesis, and Antimycobacterial Property of PEG-bis(INH) Conjugates
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Krishna Chuttani, Anil Mishra, Anjani K. Tiwari, Anupama Datta, Alka Khanna, Dipti Kakkar, and Harpal Singh
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Pharmacology ,Biodistribution ,Polymer-drug conjugates ,medicine.drug_class ,Organic Chemistry ,Isoniazid ,bacterial infections and mycoses ,Antimycobacterial ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,PEG ratio ,medicine ,Molecular Medicine ,Organic chemistry ,MTT assay ,Cytotoxicity ,Ethylene glycol ,medicine.drug ,Nuclear chemistry - Abstract
Poly(ethylene glycol) derivatives of isoniazid with varying molecular weight of poly(ethylene glycol) were designed as antimycobacterial agents. Poly(ethylene glycol)-diacrylate of three different molecular weights (MW 258, 575, and 700) was conjugated with isoniazid by the Michael addition approach. The poly(ethylene glycol)-bis(isoniazid) conjugates thus obtained were completely characterized by FT-IR, (1)H and (13)C NMR, and ESI-MS spectroscopic techniques. Comparative MTT assay of the poly(ethylene glycol)-bis(isoniazid) conjugates showed much lower cytotoxicity than the neat isoniazid. MIC studies on Mycobaterium tuberculosis H37Rv showed potential antimycobacterial activity than the free isoniazid on a molar basis. The poly(ethylene glycol)-bis(isoniazid) conjugates were successfully radiolabeled with 99m-Technetium with more than 97% efficiency and stability to assess their in vivo fate. The (99m)Tc labeled poly(ethylene glycol)-bis(isoniazid) conjugates showed higher blood retention time in New Zealand rabbits which increased with increasing molecular weight of poly(ethylene glycol). Biodistribution studies in infection-induced murine models (BALB/c mice) showed significant retention of these conjugates at the site of infection for 72 h. The results of this study illustrate the potential utility of the PEGylated isoniazid conjugates as long circulating carriers for improved antitubercular drug therapy.
- Published
- 2012
16. Synthesis of Oxovanadium(IV) Schiff base Complexes derived from C-substituted Diamines and Pyridoxal-5-Phosphate as Antitumor Agents
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Anand Kumar Pandey, Anjani K. Tiwari, Anil K. Mishra, Sudhir Chandna, Shubhra Chaturvedi, Bilikere S. Dwarakanath, and Puja Panwar Hazari
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Pharmacology ,Schiff base ,Guanine ,Stereochemistry ,Organic Chemistry ,Conjugated system ,Biochemistry ,Transplantation ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Molecular Medicine ,Chelation ,Pyridoxal phosphate ,Bifunctional ,DNA - Abstract
Oxovanadium (IV) complexes of N,N'-bispyridoxyl-5, 5'-bis (phosphate) ethylenediimine (L1) and N,N'-bis(pyridoxyl)-5,5'-bis(phosphate)-1''-(p-nitrobenzyl)ethylenediimine (L2) were synthesized by condensation of optically active C-substituted diamines and pyridoxal-5-phosphate. Oxovanadium (IV) complexes derived from L1 and L2 were evaluated as DNA cleavage agent (cleavage of supercoiled plasmid pBR322 DNA). Interestingly, both the oxovanadium (IV) complexes exhibited DNA nuclease activity, and the extent of oxidation of DNA by these vanadyl complexes was superior to VOSO(4) . The significant reduction in primary tumor and increased delay in tumor growth of 15 days was seen in the tumor regression analysis with oxovanadium (IV) complex of L1. With the preliminary studies performed with the pyridoxal-5-phosphate -based salen derivatives including the cytotoxicity and tumor regression, it is evident that the salen bifunctional chelating agent has obtained therapeutic potential if conjugated to a gene-specific targeting molecule for the oxidation of guanine residue.
- Published
- 2012
17. Kinetics of Formation for Lanthanide (III) Complexes of DTPA-(Me-Trp)2 used as Imaging Agent
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Deepa Sinha, Dipti Kakkar, Anupama Datta, Anil K. Mishra, and Anjani K. Tiwari
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Pharmacology ,Lanthanide ,Chemistry ,Ligand ,MRI contrast agent ,Organic Chemistry ,Analytical chemistry ,Protonation ,Nuclear magnetic resonance spectroscopy ,Biochemistry ,chemistry.chemical_compound ,Reaction rate constant ,Ionic strength ,Amide ,Drug Discovery ,Molecular Medicine ,Nuclear chemistry - Abstract
Diethlenetriamine-N,N,N'N''N''-pentaacetic acid (DTPA)-bis (amide) analogs have been synthesized and evaluated as a potential biomedical imaging agents. Imaging and biodistribution studies were performed in mice that showed a significant accumulation of DTPA analogs in brain. The stability and protonation constants of the complexes formed between the ligand [DTPA-(Me-Trp)(2)] and Gd(3+), Eu(3+), and Cu(2+) have been determined by pH potentiometry (Gd(3+), Eu(3+)) and spectrophotometry (Cu(2+)) at 25 °C and at constant ionic strength maintained by 0.10 M KCl. The kinetic inertness of Gd [DTPA-(Me-Trp)(2)] was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Eu(3+) exchange, a second-order [H(+)] dependence was found for the pseudo-first-order rate constant [k(0) = (4.5 ± 1.2) × 10(-6)/s; k(1) = 0.58 ± 0.1 /M/s, k(2) = (6.6 ± 0.2) × 10(4) /M(2)/s, k(3) = (4.8 ± 0.8) × 10(-4) /M/s]. In the Eu(3+) exchange, at pH
- Published
- 2011
18. Quantitative Structure Activity Relationship Study of 2,4,6-Trisubstituted-s-triazine Derivatives as Antimalarial Inhibitors of Plasmodium Falciparum Dihydrofolate Reductase
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Rita Kakkar, Himanshu Ojha, Anjani K. Tiwari, Mallika Pathak, and Pragya Gahlot
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Pharmacology ,Quantitative structure–activity relationship ,Correlation coefficient ,biology ,Stereochemistry ,Organic Chemistry ,Quantitative structure ,Plasmodium falciparum ,biology.organism_classification ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Molecular descriptor ,Drug Discovery ,Dihydrofolate reductase ,biology.protein ,Molecular Medicine ,Molecule ,Triazine - Abstract
This study presents a quantitative structure activity relationships (QSAR) study on a pool of 19 bio-active s-triazine compounds. Molecular descriptors, kappa {¹κ}, chi {³χ}, x component of the dipole moment (μ(x) ), Coulson charge (q(N) ) on the nitrogen atom sandwiched between the two substituted carbons of the triazine ring, and total energy (E(T) ) obtained from AM1 calculations provide valuable information and have a significant role in the assessment of dihydrofolate reductase (DHFR) inhibitory activity of the compounds. By using the Genetic Function Approach (GFA) technique, five QSAR models have been drawn up with the help of these calculated descriptors and DHFR inhibitory activity data of the molecules. Among the obtained QSAR models presented in the study, statistically the most significant one is a four-parameter linear equation with the Lack-of-Fit value 0.5624, squared correlation coefficient R² value of 0.7697, and the squared cross-validated correlation coefficient R²(CV) value of 0.6469. The results are discussed in light of the main factors that influence the DHFR inhibitory activity.
- Published
- 2010
19. 99mTc-DTPA-Amino Acids Conjugate as Specific SPECT Pharmaceuticals for Tumor Imaging
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Shubhra Chaturvedi, Deepa Sinha, Krishna Chuttani, Gauri Shukla, Anil K. Mishra, Anjani K. Tiwari, and Harish Chandra
- Subjects
Biodistribution ,Stereochemistry ,Biochemistry ,5-Hydroxytryptophan ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Amide ,Drug Discovery ,Animals ,Humans ,Tissue Distribution ,Amino Acids ,Carcinoma, Ehrlich Tumor ,Tomography, Emission-Computed, Single-Photon ,Pharmacology ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Chemistry ,Organic Chemistry ,Radiochemistry ,Tryptophan ,Pentetic Acid ,Condensation reaction ,Amino acid ,Yield (chemistry) ,Technetium Tc 99m Pentetate ,Molecular Medicine ,Rabbits ,Radiopharmaceuticals ,Conjugate - Abstract
(99m)Tc-Diethylene triamine pentaacetic acid-bis (amide) conjugates have been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compounds were synthesized by the condensation reaction of DTPA bis(anhydride) with different l-amino acids (methyl tryptophan, and 5-hydroxy tryptophan) and were characterized on the basis of IR, NMR, and Mass spectroscopy. (99m)Tc-labeled compounds were found stable for about 24 h under physiological conditions with more than 95% radiolabeling yield. Blood kinetic studies of all these complexes showed a bi-exponential pattern as well as quick wash out from the blood circulation. The biological t(1/2)(F) and t(1/2)(S) were found to be 20 +/- 0.001 min for DTPA-(Me-Trp)(2) and 18 +/- 0.001 min for DTPA-(5HT)(2) and t(1/2) (slow) 5 h 45 min +/- 0.001, 5 h 30 +/- 0.001 min for DTPA-(Me-Trp)(2), and DTPA-(5HT)(2), respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in right thigh. Radioconjugate derived from l-5-hydroxytryptophan exhibited remarkable localization at tumor site; whereas radiotracer derived from l-methyl tryptophan shows relatively less accumulation at the tumor site. Tumor-to-muscles ratios were 5.07 +/- 0.001, and 4.2 +/- 0.001 at 1 and 4 h for (99m)Tc-DTPA-(Me trp)(2) and 4.97 +/- 0.001 and 5.8 +/- 0.001 at 1 and 4 h after postinjection for (99m)Tc-DTPA-(5HT)(2), respectively. The preliminary results with these amino acid based ligands are encouraging to carrying out further in vivo experiments for targeted tumor imaging.
- Published
- 2009
20. Quantitative Structure-Property Relationship (Correlation Analysis) of Phosphonic Acid-Based Chelates in Design of MRI Contrast Agent
- Author
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Ankur Kaul, Gauri Shukla, Himanshu Ojha, Anjani K. Tiwari, Anil K. Mishra, Anupama Dutta, Rakesh Srivastava, and Pooja Srivastava
- Subjects
Pharmacology ,Quantitative structure–activity relationship ,Models, Statistical ,Gadolinium ,MRI contrast agent ,Organic Chemistry ,Organophosphonates ,Contrast Media ,Quantitative Structure-Activity Relationship ,chemistry.chemical_element ,Magnetic Resonance Imaging ,Biochemistry ,Nuclear magnetic resonance ,chemistry ,Molecular descriptor ,Drug Discovery ,Linear regression ,Molecular Medicine ,Physical chemistry ,Molecule ,Chelation ,Chelating Agents - Abstract
Nuclear magnetic resonance imaging is a very useful tool in modern medical diagnostics, especially when gadolinium (III)-based contrast agents are administered to the patient with the aim of increasing the image contrast between normal and diseased tissues. With the use of soft modelling techniques such as quantitative structure-activity relationship/quantitative structure-property relationship after a suitable description of their molecular structure, we have studied a series of phosphonic acid for designing new MRI contrast agent. Quantitative structure-property relationship studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors of the phosphonic acid-based chelating agent and their stability constants. The final quantitative structure-property relationship mathematical models were found as--quantitative structure-property relationship Model for phosphonic acid series (Model 1)--log K(ML) = {5.00243(+/-0.7102)}- MR {0.0263(+/-0.540)}n = 12 l r l = 0.942 s = 0.183 F = 99.165 quantitative structure-property relationship Model for phosphonic acid series (Model 2)--log K(ML) = {5.06280(+/-0.3418)}- MR {0.0252(+/- .198)}n = 12 l r l = 0.956 s = 0.186 F = 99.256.
- Published
- 2009
21. Synthesis and pharmacological study of novel pyrido-quinazolone analogues as anti-fungal, antibacterial, and anticancer agents
- Author
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Aruna Bajpai, Anjani K. Tiwari, Pushpa Mishra, A. K. Mishra, Vinay Singh, R. K. Sharma, and Vinay Kumar Pandey
- Subjects
Staphylococcus aureus ,Antifungal Agents ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Anti fungal ,Antineoplastic Agents ,Adenocarcinoma ,Biochemistry ,Chemical synthesis ,Structure-Activity Relationship ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Drug Discovery ,Humans ,Structure–activity relationship ,Cytotoxicity ,Molecular Biology ,Cell Proliferation ,Antibacterial agent ,Molecular Structure ,Chemistry ,Organic Chemistry ,In vitro ,Anti-Bacterial Agents ,Klebsiella pneumoniae ,Aspergillus ,Pseudomonas aeruginosa ,Quinazolines ,Lactam ,Molecular Medicine - Abstract
A versatile method for novel pyrido-quinazolones was described here and tested for anti-fungal, antibacterial, and anticancerous activities. These synthesized compounds were characterized on the basis of spectroscopic techniques and evaluated for specific radiopharmaceuticals. Preliminary radiolabeling results with (99m)Tc and biological evaluation studies showed promising results for further evaluation in vivo. The efficiency of labeling was more than 98% and complexes were stable for about 18 h at 25 degrees C in the presence of serum.
- Published
- 2006
22. Bis(methylpyridine)-EDTA derivative as a potential ligand for PET imaging: synthesis, complexation, and biological evaluation
- Author
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Swati Aggarwal, Anjani K. Tiwari, Vikas Kumar, Anil K. Mishra, Pooja Singh, Ramendra Pratap, and Krishna Chuttani
- Subjects
Biodistribution ,Stereochemistry ,Pyridines ,Metal ions in aqueous solution ,Contrast Media ,Gallium ,Ligands ,Biochemistry ,chemistry.chemical_compound ,Mice ,Coordination Complexes ,Drug Discovery ,Pyridine ,medicine ,Animals ,Humans ,Tissue Distribution ,Edetic Acid ,Serum Albumin ,Pharmacology ,Mice, Inbred BALB C ,Chemistry ,Organic Chemistry ,Hydrogen Bonding ,Ligand (biochemistry) ,Human serum albumin ,Binding constant ,Kinetics ,Stability constants of complexes ,Positron-Emission Tomography ,Lipophilicity ,Molecular Medicine ,Rabbits ,Nuclear chemistry ,medicine.drug ,Protein Binding - Abstract
A novel transitional metal ligand derivatized from EDTA-conjugated 2-amino-4-methyl pyridine, an acyclic vehicle (EDTA-Mepy2 ) was designed, synthesized, and characterized for PET imaging with ⁶⁸Ga. The drug likeliness and appropriate lipophilicity were first analyzed by molecular docking studies which shows interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at Lys199, Arg257, and His242 residues, which make it more appropriate in transportation as a specific ligand for PET imaging. As a confirmation, binding constant of the ligand with human serum albumin was calculated at λex = 350 nm which was found to be 4.9 × 10³ m⁻¹. The pharmacokinetics of (68) Ga-EDTA-Mepy2 was analyzed by blood kinetics (t(1/2) slow: 3 h 56 min and t(1/2) fast: 32 min) and biodistribution (maximum % ID/g was found in kidney at 1 h). Further the capability of this ligand was analyzed as optical marker also, by recording λex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λem = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15-20 times selectivity over the endogenously present metal ions (KG aL /KZ nL = 14.3, KG aL /KC uL = 18.1).
- Published
- 2014
23. Synthesis, biological evaluation and molecular docking studies of high-affinity bone targeting N,N(') -bis (alendronate) diethylenetriamene-N,N'-triacetic acid: a bifunctional bone scintigraphy agent
- Author
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Nidhi Chadha, Deepa Sinha, Anil K. Mishra, Krishna Chuttani, and Anjani K. Tiwari
- Subjects
Biodistribution ,Geranylgeranyl pyrophosphate ,Stereochemistry ,medicine.medical_treatment ,Acetates ,Biochemistry ,Bone and Bones ,Cell Line ,chemistry.chemical_compound ,Mice ,Farnesyl diphosphate synthase ,Drug Discovery ,medicine ,Animals ,Humans ,Tissue Distribution ,Pharmacology ,Mice, Inbred BALB C ,biology ,medicine.diagnostic_test ,Organic Chemistry ,Bisphosphonate ,Molecular Docking Simulation ,Bone scintigraphy ,chemistry ,Docking (molecular) ,biology.protein ,Osteocalcin ,Molecular Medicine ,Rabbits ,Conjugate ,Half-Life - Abstract
A bisphosphonate derivative DTPA-bis(alendronate) conjugate has been synthesized and evaluated as potential radiopharmaceutical for bone imaging. The compound was synthesized by the covalent coupling of DTPA-bis(anhydride) with alendronate and was char-acterized on the basis of IR, NMR and mass spectroscopy. It was labelled with (99m) Tc with 96% efficacy and was found stable for about 24 h under physiological conditions. Blood kinetic studies of (99m) Tc DTPA-bis(alendronate) showed a biexponential pattern as well as quick washout from the blood circulation. The biological t1/2 (F) and t1/2 (S) were found to be 50 min ± 0.001 and 6 h 30 min ± 0.005, respectively. Imaging and biodistribution studies showed a significant accumulation of (99m) Tc DTPA-bis(alendronate) conjugate at bone site. Bone-to-muscles ratios were 12.08 ± 0.001 at 1 h, 45.33 ± 0.001 at 4 h and 35.83 ± 0.001 at 24 h after post-injection, respectively. The receptor binding of the (99m) Tc-DTPA-bis (alendronate) was established on human bone cell line (Soas-2) revealed KD = 0.86 nm. The preliminary result of the (99m) Tc-DTPA-bis(alendronate) is encouraging to carrying out further in vivo experiment for targeted bone imaging because of good-bone-to-normal-organ contrast. Further docking analysis with molecular targets, farnesyl diphosphate synthase, geranylgeranyl pyrophosphate and osteocalcin revealed the high affinity of -17.419 and thus represents strong potential of bone-imaging agent.
- Published
- 2013
24. Synthesis and biological evaluation of newly designed phosphonate based bone-seeking agent
- Author
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Anil K. Mishra, Anjani K. Tiwari, Krishna Chuttani, Pooja Srivastava, and Nidhi Chadha
- Subjects
Models, Molecular ,Stereochemistry ,Protein Data Bank (RCSB PDB) ,Gallium Radioisotopes ,Ligands ,Bone and Bones ,chemistry.chemical_compound ,Heterocyclic Compounds, 1-Ring ,Mice ,Organophosphorus Compounds ,Drug Discovery ,Animals ,Chelation ,Tissue Distribution ,Bifunctional ,Radionuclide Imaging ,Biological evaluation ,Chelating Agents ,Pharmacology ,Mice, Inbred BALB C ,biology ,Molecular Structure ,Organic Chemistry ,General Medicine ,Organotechnetium Compounds ,Ligand (biochemistry) ,Phosphonate ,chemistry ,Stability constants of complexes ,Organ Specificity ,Drug Design ,Osteocalcin ,biology.protein ,Rabbits ,Radiopharmaceuticals ,Nuclear chemistry - Abstract
A cyclic tetraaza based bifunctional triphosphonate ligand 10-(2-aminoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris(methylenephosphonic acid) (DO3MP-EA) was synthesized as bone-seeking theranostic agent. The compound was characterized by spectroscopic techniques and labelled with 99m Tc with more than 97% purity. Blood clearance of 99mTc labelled compound a quick wash out from the circulation. The compound was excreted mainly via kidneys and accumulation of 99m Tc-DO3MP-EA in bone was 9.53 ± 1.06% of injected dose per gram of bone at 1 h. The preliminary CADD analysis confirms the efficacy of DO3MP-EA (G Score −7.005) as better binding agent for osteocalcin (pdb 1Q8H) rather than other known clinical agents. Subsequently stability constant of chelate with Ga(III) was found to be 18.6 which confirms its efficacy as 68 Ga labelled PET radiopharmaceutical for bone.
- Published
- 2012
25. Disubstituted 4(3H) quinazolones: a novel class of antitumor agents
- Author
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Vinay Kumar Singh, Rajbala Sharma, Rakesh Srivastava, Anjani K. Tiwari, Vikas Srivastava, Himanshu Sharma, and Anand Mohan Srivastava
- Subjects
Pharmacology ,Semicarbazide ,Stereochemistry ,Organic Chemistry ,Quantitative Structure-Activity Relationship ,Antineoplastic Agents ,Mass spectrometry ,Biochemistry ,Combinatorial chemistry ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Pyridine ,Anthranilic acid ,Quinazoline ,Quinazolines ,Molecular Medicine ,Moiety ,Humans ,Drug Screening Assays, Antitumor - Abstract
A series of disubstituted 4(3H) quinazolines were designed for potential application in tumors. Firstly, N-benzoyl anthranilic acid is formed, which undergoes cyclization in the presence of pyridine. Subsequently, nucleophilic attack by semicarbazide on the carbonyl carbon gives 2-substituted 3-carbamido 4(3H) quinazolones, which gives final compound with appropriate substitution. The final as well as intermediate products were confirmed by NMR, FT-IR, and mass spectrometry. In vitro toxicity was performed with different cell lines and showed that the connection of hydrophilic styryl to quinazoline moiety increases its efficacy.
- Published
- 2009
26. Effect of a novel series of benzothiazolo-quinazolones on epidermal growth factor receptor (EGFR) and biological evaluations
- Author
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Anjani K. Tiwari, Vinay Singh, Gauri Shukla, Aruna Bajpai, Harish Chandra, and Anil K. Mishra
- Subjects
Microbial Sensitivity Tests ,Biochemistry ,Potassium carbonate ,Acetic acid ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Mice ,In vivo ,Potassium thiocyanate ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Epidermal growth factor receptor ,Benzothiazoles ,Pharmacology ,chemistry.chemical_classification ,biology ,Organic Chemistry ,Aromatic amine ,Technetium ,ErbB Receptors ,chemistry ,Benzothiazole ,Cell culture ,Isotope Labeling ,biology.protein ,Quinazolines ,Molecular Medicine - Abstract
A newly designed benzothiazolo-quinazolone series was synthesized by an aromatic amine and potassium thiocyanate in the presence of bromine in glacial acetic acid, and the final product was obtained by subsequent reaction with 5-arylamido/imidoalkyl-2-chlorobenzoic acid in the presence of potassium carbonate and further cyclization with sulphuric acid. A preliminary radiolabelling study with technetium shows a promising potential for further in vivo evaluation. Anti-bacterial, anti-viral and anti-tumor activities were evaluated for biological properties. Lead compounds are able to block epidermal growth factor receptor (EGFR) in human breast adenocarcinoma cell line, MCF-7.
- Published
- 2008
27. Synthesis, characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde
- Author
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Deepa Sinha, Sweta Singh, Harish Chandra, Anjani K. Tiwari, Anil Mishra, Pushpa Mishra, and Gauri Shukla
- Subjects
Indoles ,Stereochemistry ,Glutamic Acid ,Chemical synthesis ,chemistry.chemical_compound ,Mice ,Valine ,Neoplasms ,Drug Discovery ,Aspartic acid ,Animals ,Humans ,Histidine ,Tissue Distribution ,Schiff Bases ,Antibacterial agent ,Pharmacology ,Indole test ,Schiff base ,Bacteria ,Chemistry ,Organic Chemistry ,Fungi ,Technetium ,General Medicine ,Thin-layer chromatography ,Rabbits ,Half-Life - Abstract
Eight novel heterocyclic Schiff bases derived from the condensation reactions of indole 3-carboxaldehyde with different l-amino acids (histidine, glutamic acid, aspartic acid, leucine, valine) as well as with some aminophenols, have been synthesized and characterized by various spectroscopic methods (IR, MS, (1)H NMR). Schiff base derivatives of indole 3-carboxaldehyde were labeled with (99m)Tc and radiochemical purity was above 97% which is ascertained by instant thin layer chromatography using different solvent conditions. Stability studies of all the derivatives of indole 3-carboxaldehyde was determined under physiological conditions and were stable for more than 24h. Blood clearance showed a quick wash out from the circulation and biological half life was found to be t((1/2))(F)=1h 15min; t((1/2))(S)=10h 05min. Excellent quality radioimages of tumor bearing mice were recorded showing rapid clearance of background activity, visualization of tumor at 3h and clearance from kidneys of histidine analogue which was further evidenced in biodistribution studies. Antimicrobial activity of these Schiff base compounds was evaluated against Bacillus subtilis, Pseudomonas fluorescence, Staphylococcus aureus, Aspergillus niger, Candida albicans and Trichophyton rubrum.
- Published
- 2007
28. Synthesis and evaluation of novel benzimidazole derivative [Bz-Im] and its radio/biological studies
- Author
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Pushpa Mishra, Sweta Singh, Deepa Sinha, Anjani K. Tiwari, Vartika Singh, Aruna Bajpai, and Anil K. Mishra
- Subjects
Biodistribution ,Benzimidazole ,Antifungal Agents ,Stereochemistry ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Biochemistry ,Chemical synthesis ,Cholecystokinin receptor ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,In vivo ,Drug Discovery ,medicine ,Animals ,Molecular Biology ,Organic Chemistry ,Biological activity ,Receptor antagonist ,In vitro ,Receptor, Cholecystokinin B ,chemistry ,Molecular Medicine ,Benzimidazoles ,Receptors, Cholecystokinin ,Aspergillus niger ,Rabbits ,Radiopharmaceuticals - Abstract
Two different benzimidazole analogues act as multimodal agent, first one as novel non-peptidic CCK-B receptor antagonist and similarly as potent anti-fungal agent, designated as [Bz-Im]. These compounds were synthesized and characterized by spectroscopic techniques such as FT-IR, NMR, EI-MS and also evaluated for specific radiopharmaceuticals. Preliminary radiolabeling results with (99m)Tc and biological evaluation studies showed promising results for further evaluation in vivo. The efficiency of labeling was more than 97% and complex was stable for about 12h at 30 degrees C in the presence of serum. Both ligands showed binding to most of the organs, known to express CCK receptors in biodistribution studies. Cholecystokinin (CCK(1) andCCK(2)) receptor binding affinities of these analogues are, IC(50), 0.942+/-0.107 for compound C and 0.665+/-0.211 for compound D in rat pancreatic acini. The anti-fungal activity has shown inhibitory activity against Aspergillus flavus and Aspergillus niger. These studies have provided a new template for further development of non-peptidic ligands for diagnostic and therapeutic purposes of diseases related with CCK receptors as well as anti-microbes.
- Published
- 2006
29. Perception into hypoxia selectivity and electronic features of symmetrically substituted bisthiosemicarbazone ligands and their copper complexes: DFT and QM/MM docking
- Author
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Vikas Kumar, Nidhi Chadha, Anjani K. Tiwari, Anil K. Mishra, and Marilyn Daisy Milton
- Subjects
Pharmacology ,Chemistry ,Organic Chemistry ,Pharmaceutical Science ,chemistry.chemical_element ,Biochemistry ,Copper ,QM/MM ,Crystallography ,Delocalized electron ,Computational chemistry ,Docking (molecular) ,Drug Discovery ,Molecular Medicine ,Molecule ,Selectivity ,Natural bond orbital - Abstract
Bisthiosemicarbazone ligands and copper complexes, a promising class of molecules for imaging, have been studied by DFT/MO6 theory with NBO analysis to reveal strong delocalization. To shed light into the aspects of hypoxia selectivity of complexes was inferred from binding of copper complexes with HIF-1α by QM/MM docking. The affinity of copper complexes cross-validated by force filed analysis.
- Published
- 2013
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