Faculty Publications
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Item Synthesis and anti-inflammatory evaluation of some new 3,6-disubstituted-1, 2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles bearing pyrazole moiety(2012) Malladi, S.; Isloor, A.M.; Shetty, P.; Fun, H.-K.; Telkar, S.; Mahmood, R.; Isloor, N.In the present study, a new series of 3,6-disubstituted- 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles (4aj) have been synthesized by condensing 3-substituted-4-amino-5- mercapto-1,2,4-triazoles (1a-b) with various 3-substitutedpyrazole- 4-carboxylic acids (3a-e) in the presence ofPOCl3. The structures of newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13CNMR, and mass spectroscopic studies. Structure of the compound 4b was also confirmed by recording the single crystal X-ray structure. All the synthesized compounds were screened for their anti-inflammatory activities by carrageenan induced paw edema method. Anti-inflammatory screening indicated that, compounds 4d, 4e, and 4h were found to be biologically active whereas remaining compounds showed poor antiinflammatory activity. Also molecular docking studies were also performed for compounds which showed good antiinflammatory activity. © Springer Science+Business Media, LLC 2011.Item New INH-pyrazole analogs: Design, synthesis and evaluation of antitubercular and antibacterial activity(Elsevier Ltd, 2015) Nayak, N.; Ramprasad, J.; Udayakumar, U.With the aim of developing promising antitubercular and antibacterial leads, we have designed and synthesized a new series of isonicotinohydrazide based pyrazole derivatives (5a-r). All new derivatives (4a-b and 5a-r) were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) strain. Four compounds 5j, 5k, 5l and 4b emerged as promising antitubercular agents with MIC of ?4.9 ?M which is much lower than the MIC of the first line antitubercular drug, ethambutol. The 3-chlorophenyl substituent at position-3 of the pyrazole ring enhanced the antiTB activity of the molecules. Three derivatives 5b, 5k and 4b exhibited promising antibacterial activity against the tested bacterial strains. The active molecules were nontoxic to normal Vero cells and showed high selectivity index (>160). The structure and antitubercular activity relationship was further supported by in silico molecular docking study of the active compounds against enoyl acyl carrier protein reductase (InhA) enzyme of M. tuberculosis. © 2015 Published by Elsevier Ltd.Item An Integrated Approach of CNT Front-end Amplifier towards Spikes Monitoring for Neuro-prosthetic Diagnosis(SpringerOpen, 2018) Kumar, S.; Kim, B.-S.; Song, H.The future neuro-prosthetic devices would be required spikes data monitoring through sub-nanoscale transistors that enables to neuroscientists and clinicals for scalable, wireless and implantable applications. This research investigates the spikes monitoring through integrated CNT front-end amplifier for neuro-prosthetic diagnosis. The proposed carbon nanotube-based architecture consists of front-end amplifier (FEA), integrate fire neuron and pseudo resistor technique that observed high electrical performance through neural activity. A pseudo resistor technique ensures large input impedance for integrated FEA by compensating the input leakage current. While carbon nanotube based FEA provides low-voltage operation with directly impacts on the power consumption and also give detector size that demonstrates fidelity of the neural signals. The observed neural activity shows amplitude of spiking in terms of action potential up to 80 ?V while local field potentials up to 40 mV by using proposed architecture. This fully integrated architecture is implemented in Analog cadence virtuoso using design kit of CNT process. The fabricated chip consumes less power consumption of 2 ?W under the supply voltage of 0.7 V. The experimental and simulated results of the integrated FEA achieves 60 G? of input impedance and input referred noise of 8.5 nv/Hzover the wide bandwidth. Moreover, measured gain of the amplifier achieves 75 dB midband from range of 1 KHz to 35 KHz. The proposed research provides refreshing neural recording data through nanotube integrated circuit and which could be beneficial for the next generation neuroscientists. © 2018, The Korean BioChip Society and Springer-Verlag GmbH Germany, part of Springer Nature.Item Impact of coronary tortuosity on the artery hemodynamics(Elsevier Sp. z o.o., 2020) Buradi, A.; Mahalingam, A.The presence of tortuosity in coronary artery (CA) affects the local wall shear stress (WSS) which is an influencing hemodynamic descriptor (HD) for the development of atherosclerotic sites. To conduct a morphological parametric study in coronary arteries (CAs), several idealized tortuous artery models were obtained by varying three morphological indices namely, curvature radius (CR), distance between two bends (DBB) and the angle of bend (AoB). Computational fluid dynamics methodology with multiphase mixture theory is used to explore the effect of coronary tortuosity on various WSS based hemodynamic descriptors (HDs) namely, time-averaged WSS, oscillatory shear index, time-averaged WSS gradient, endothelial cell activation potential and the relative residence time that are used to determine the vulnerable locations for the onset of thrombosis and atherosclerosis. Our findings suggest that all the tortuosity morphological indices, CR, DBB and AoB have significant influence on the distributions of various HDs and hemodynamics. It is also observed that atherosclerosis prone sites were witnessed at the inner artery wall at downstream regions of the bend section 1 and bend section 2 in all the tortuous artery models studied and found to increase as the CR and DBB were reduced however, found to increase as the AoB is increased. Hence, severe coronary tortuosity in CAs with small CR, small DBB and higher AoB may have lower WSS zones at inner bend sections which promote atherosclerosis plaque progression. The analysis obtained from this multiphase blood flow study can be employed potentially in the clinical assessment on the severity of atherosclerosis lesions as well as in understanding the underlying mechanisms of localization and formation of atherosclerotic plaques. © 2019 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of SciencesItem Computational analysis of therapeutic enzyme uricase from different source organisms(Bentham Science Publishers P.O. Box 294 Bussum 1400 AG, 2020) Nelapati, A.K.; JagadeeshBabu, J.Background: Hyperuricemia and gout are the conditions, which is a response of accumulation of uric acid in the blood and urine. Uric acid is the product of purine metabolic pathway in humans. Uricase is a therapeutic enzyme that can enzymatically reduces the concentration of uric acid in serum and urine into more a soluble allantoin. Uricases are widely available in several sources like bacteria, fungi, yeast, plants and animals. Objective: The present study is aimed at elucidating the structure and physiochemical properties of uricase by insilico analysis. Methods: A total number of sixty amino acid sequences of uricase belongs to different sources were obtained from NCBI and different analysis like Multiple Sequence Alignment (MSA), homology search, phylogenetic relation, motif search, domain architecture and physiochemical properties including pI, EC, Ai, Ii, and were performed. Results: Multiple sequence alignment of all the selected protein sequences has exhibited distinct difference between bacterial, fungal, plant and animal sources based on the position-specific existence of conserved amino acid residues. The maximum homology of all the selected protein sequences is between 51-388. In singular category, homology is between 16-337 for bacterial uricase, 14-339 for fungal uricase, 12-317 for plants uricase, and 37-361 for animals uricase. The phylogenetic tree constructed based on the amino acid sequences disclosed clusters indicating that uricase is from different source. The physiochemical features revealed that the uricase amino acid residues are in between 300-338 with a molecular weight as 33-39kDa and theoretical pI ranging from 4.95-8.88. The amino acid composition results showed that valine amino acid has a high average frequency of 8.79 percentage compared to different amino acids in all analyzed species. Conclusion: In the area of bioinformatics field, this work might be informative and a stepping-stone to other researchers to get an idea about the physicochemical features, evolutionary history and structural motifs of uricase that can be widely used in biotechnological and pharmaceutical industries. Therefore, the proposed in silico analysis can be considered for protein engineering work, as well as for gout therapy. © 2020 Bentham Science Publishers.Item The bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazoles(Elsevier Ltd, 2020) Reddyrajula, R.; Udayakumar, U.Tuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyrazinamide structure using bioisosterism and rational approaches by incorporating the 1,2,3-triazole moiety. Three sets of pyrazine-1,2,3-triazoles (3a-o, 5a-o and 9a-l) are designed, synthesized and evaluated for their in vitro inhibitory potency against mycobacterium tuberculosis H37Rv. The pyrazine-1,2,3-triazoles synthesized through the bioisosteric modification displayed improved activity as compared to rationally modified pyrazine-1,2,3-triazoles. Among 42 title compounds, seven derivatives demonstrated significant anti-tubercular activity with the MIC of 1.56 ?g/mL, which are two-fold more potent than the parent compound pyrazinamide. Further, the synthesized pyrazinamide analogs demonstrated moderate inhibition activity against several bacterial strains and possessed an acceptable in vitro cytotoxicity profile as well. Additionally, the activity profile of pyrazine-1,2,3-triazoles was validated by performing the molecular docking studies against the Inh A enzyme. Furthermore, in silico ADME prediction revealed good oral bioavailability for the potent molecules. © 2019 Elsevier LtdItem Computational investigation of hydrodynamics and drying of industrial sludge waste in a spouted bed column(Scientific Publishers, 2020) Santhosh Kumar, N.; Ali, B.The disposal of sludge from waste water treatment plants adversely affects the environment. Since sludge wastes are sticky, drying of such waste water sludge is challenging. Conventionally, these sludges are dried in open spaces where a large area of land is required which is a time-consuming process. To overcome this, spouted bed is used in the present investigation. The spouted bed is a gas-solid contactor for handling coarse particles of size greater than 1 mm with low operating pressure. In this work, hydrodynamics of waste water sludge in a conventional spouted bed is numerically investigated using Computational Fluid Dynamics (CFD). Euler-Eulerian CFD model is used to study the flow pattern in such system. The continuous phase turbulence (air) is modeled using standard - model. The spouting height and solid circulation rate are calculated to analyze spouting behavior. This is compared with a draft tube spouted bed system and found that the draft tube supports in enhancing the spouting characteristics of the bed. Further, an optimum draft tube configuration is found that promotes solid circulation rate. The drying characteristics are analyzed for various operating conditions and found that the temperature of air significantly improves the rate of drying. © 2020 Scientific Publishers. All rights reserved.Item Molecular mechanism of inhibition of COVID-19 main protease by ?-adrenoceptor agonists and adenosine deaminase inhibitors using in silico methods(Taylor and Francis Ltd., 2022) Venugopal, P.P.; Chakraborty, D.Novel coronavirus (COVID-19) responsible for viral pneumonia which emerged in late 2019 has badly affected the world. No clinically proven drugs are available yet as the targeted therapeutic agents for the treatment of this disease. The viral main protease which helps in replication and transcription inside the host can be an effective drug target. In the present study, we aimed to discover the potential of ?-adrenoceptor agonists and adenosine deaminase inhibitors which are used in asthma and cancer/inflammatory disorders, respectively, as repurposing drugs against protease inhibitor by ligand-based and structure-based virtual screening using COVID-19 protease-N3 complex. The AARRR pharmacophore model was used to screen a set of 22,621 molecules to obtain hits, which were subjected to high-throughput virtual screening. Extra precision docking identified four top-scored molecules such as +/?-fenoterol, FR236913 and FR230513 with lower binding energy from both categories. Docking identified three major hydrogen bonds with Gly143, Glu166 and Gln189 residues. 100 ns MD simulation was performed for four top-scored molecules to analyze the stability, molecular mechanism and energy requirements. MM/PBSA energy calculation suggested that van der Waals and electrostatic energy components are the main reasons for the stability of complexes. Water-mediated hydrogen bonds between protein-ligand and flexibility of the ligand are found to be responsible for providing extra stability to the complexes. The insights gained from this combinatorial approach can be used to design more potent and bio-available protease inhibitors against novel coronavirus. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.Item Control force and inertial migration in Poiseuille flow: a computational study(Taylor and Francis Ltd., 2023) Neeraj, M.P.; Maniyeri, R.The present work deals with the development of a numerical model to analyze the effect of control force on a single rigid massive cylindrical particle’s lateral migration in a straight channel. The finite volume immersed boundary method (feedback forcing-based), along with semi-implicit strategy, is incorporated to create a computational model. The control force is applied in the direction against the fluid flow, to control the equilibrium position and drive it to the channel center. The effect of the Reynolds number, particle diameter and density ratio on the control force is studied. From parametric studies, a prediction model is developed for the control force with the Reynolds number, particle diameter and density ratio as inputs. The linear regression methodology in machine learning is utilized to create the prediction model. The predicted values of control force are observed to match those of the simulation results. © 2023 Taylor & Francis Group, LLC.Item Discovery of 1,2,3-triazole incorporated indole-piperazines as potent antitubercular agents: Design, synthesis, in vitro biological evaluation, molecular docking and ADME studies(Elsevier Ltd, 2024) Reddyrajula, R.; Etikyala, U.; Vijjulatha, V.; Udayakumar, U.In this report, a library consisting of three sets of indole-piperazine derivatives was designed through the molecular hybridization approach. In total, fifty new hybrid compounds (T1-T50) were synthesized and screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Five (T36, T43, T44, T48 and T49) among fifty compounds exhibited significant inhibitory potency with the MIC of 1.6 µg/mL, which is twofold more potent than the standard first-line TB drug Pyrazinamide and equipotent with Isoniazid. N-1,2,3-triazolyl indole-piperazine derivatives displayed improved inhibition activity as compared to the simple and N-benzyl indole-piperazine derivatives. In addition, the observed activity profile of indole-piperazines was similar to standard anti-TB drugs (isoniazid and pyrazinamide) against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains, demonstrating the compounds’ selectivity towards the Mycobacterium tuberculosis H37Rv strain. All the active anti-TB compounds are proved to be non-toxic (with IC50 > 300 μg/mL) as verified through the toxicity evaluation against VERO cell lines. Additionally, molecular docking studies against two target enzymes (Inh A and CYP121) were performed to validate the activity profile of indole-piperazine derivatives. Further, in silico-ADME prediction and pharmacokinetic parameters indicated that these compounds have good oral bioavailability. © 2023 Elsevier Ltd