Publications by authors named "N Suchetha Kumari"

583 Publications

Pd-Catalysed [3 + 2]-cycloaddition towards the generation of bioactive bis-heterocycles/identification of COX-2 inhibitors analysis.

Org Biomol Chem 2022 May 25. Epub 2022 May 25.

School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, NH-8, Ajmer-305801, Rajasthan, India.

In the current research, we envisaged the synthesis of bis-heterocycles containing the dihydroisoxazole ring by [3 + 2] cycloaddition of VECs (vinyl ethylene carbonates) and nitrile oxides, assisted by a Pd catalyst. Herein we explored hydroximoyl chlorides as versatile precursors for the generation of nitrile oxides that were exploited to achieve the cycloaddition reaction on a vinyl group of VECs to generate bis-heterocycles. -based studies of bis-heterocycles on the cyclooxygenase (COX) enzyme displayed selective COX-2 inhibition.
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http://dx.doi.org/10.1039/d2ob00467dDOI Listing
May 2022

Genome-wide identification of carbapenem-resistant Gram-negative bacterial (CR-GNB) isolates retrieved from hospitalized patients in Bihar, India.

Sci Rep 2022 May 19;12(1):8477. Epub 2022 May 19.

Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Carbapenemase-producing clinical isolates are becoming more common over the world, posing a severe public health danger, particularly in developing nations like India. Carbapenem-resistant Gram-negative bacterial (CR-GNB) infection has become a fast-expanding global threat with limited antibiotic choice and significant mortality. This study aimed to highlight the carbapenem-resistance among clinical isolates of hospital admitted patients in Bihar, India. A cross-sectional study was conducted with 101 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. All GNB isolates were tested for their antimicrobial susceptibility using Kirby-Bauer disc diffusion method. Double disc synergy test / modified Hodge test (DDST/MHT) were used to detect carbapenemase production by these isolates. Subsequently, these isolates were evaluated for carbapenem-resistance genes using whole-genome sequencing method. The overall percentage of carbapenem-resistance among GNB was (17/101) 16.8%. The genomic analysis of antimicrobial-resistance (AMR) demonstrates a significantly high prevalence of bla followed by bla, bla, bla and bla β-lactam or carbapenem resistance genes among clinical isolates of GNB. Co-occurrence of bla with other beta-lactamase-encoding genes was found in 70.6% of carbapenemase-producing isolates. Our study highlights the mechanism of carbapenem-resistance to curb the overwhelming threat posed by the emergence of drug-resistance in India.
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http://dx.doi.org/10.1038/s41598-022-12471-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120164PMC
May 2022

Feasibility, acceptability and evaluation of meditation to augment Yoga practice among persons diagnosed with schizophrenia.

Acta Neuropsychiatr 2022 May 19:1-37. Epub 2022 May 19.

Department of Psychiatry, Centre of Excellence in Mental Health, Atal Bihari Vajpayee Institute of Medical Sciences-Dr. Ram Manohar Lohia Hospital, New Delhi, India.

Objective: To design a meditation protocol and test its feasibility, acceptability and efficacy in conjunction with YT for persons with schizophrenia (SZ).

Methods: The meditation protocol consisted of Anapana (observing normal respiration) and Yoga Nidra (supine, restful awareness). In a single blind randomized controlled trial, medicated and clinically stable outpatients diagnosed with SZ were randomized to receive treatment as usual (TAU), TAU augmented with yoga training (YT), or TAU augmented with meditation and yoga training (MYT) for three weeks (N=145). Acceptability, clinical, social and cognitive functions were assessed after 3 weeks and 3 months post randomization using within group and between groups analyses with repeated measures multivariate tests.

Results: No group-wise differences in compliance, study discontinuation, major/serious side effects or adverse events were noted. For six assessed clinical variables, the direction of changes were in the desired direction and the effect sizes were greater in the MYT group compared with the TAU group at both time points. Changes in social function variables were greater at 3 months than at 3 weeks. Nominally significant improvement in individual cognitive domains were noted in all groups at both time points. All effect sizes were in the small to medium range.

Conclusion: MYT is feasible, acceptable and shows modest benefits for persons with SZ. MYT can also improve quality of life and clinical symptoms. Larger studies of longer duration are warranted.
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http://dx.doi.org/10.1017/neu.2022.14DOI Listing
May 2022

Adjuvant role of a T-type calcium channel blocker, TTA-A2, in lung cancer treatment with paclitaxel.

Cancer Drug Resist 2021 14;4(4):996-1007. Epub 2021 Nov 14.

Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Hyderabad 502285, India.

Chemoresistance is a prevalent issue in cancer treatment. Paclitaxel (PTX) is a microtubule-binding anticancer drug used in various cancer treatments. However, cancer cells often show chemoresistance against PTX with the help of P-glycoprotein (Pgp) - a drug efflux pump. It has also been observed that overexpressed T-type calcium channels (TTCCs) maintain calcium homeostasis in cancer cells, and calcium has a role in chemoresistance. Therefore, the aim of this study was to test the adjuvant role of TTA-A2, a TTCC blocker, in enhancing the anticancer effect of PTX on the A549 lung adenocarcinoma cell line. Morphology assay, calcium imaging assay, clonogenic assay, apoptosis assay, and real-time polymerase chain reaction (real-time PCR) were performed to find the adjuvant role of TTA-A2. Samples were treated with PTX at 10 nM concentration and TTA-A2 at 50 and 100 nM concentrations. PTX and TTA-A2 were used in the combination treatment at 10 and 100 nM concentrations, respectively. Immunocytochemistry confirmed the expression of TTCC in A549 cells. Morphology assay showed altered morphology of A549 cells. The adjuvant role of TTA-A2 was observed in the calcium imaging assay in spheroids, in the clonogenic assay in monolayers, and in the apoptosis assay in both cultures. With real-time PCR, it was observed that, even though cells express the mRNA of Pgp, it is non-significant upon treatment with PTX and TTA-A2. TTA-A2 can be used as an adjuvant to reduce chemoresistance in cancer cells as well as to enhance the anticancer effect of the standard anticancer drug PTX. Being a potent TTCC inhibitor, TTA-A2 may also enhance the anticancer effects of other anticancer drugs.
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http://dx.doi.org/10.20517/cdr.2021.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992437PMC
November 2021

Rationalizing the Use of Polyphenol Nano-formulations in the Therapy of Neurodegenerative Diseases.

CNS Neurol Disord Drug Targets 2022 May 12. Epub 2022 May 12.

Kirorimal College, University of Delhi, Delhi, India.

Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of β- synuclein in the neurons are the hallmark of Parkinson's disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while LDOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current treatment for these NDs is limited due to the blood-brain barrier (BBB) that hinders drug targeting towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with anti-inflammatory properties to the site of action.
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http://dx.doi.org/10.2174/1871527321666220512153854DOI Listing
May 2022
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