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Article ; Online: Deletion of Dictyostelium tpc2 gene forms multi-tipped structures, regulates autophagy and cell-type patterning.

Rathore, Madhubala / Thakur, Ashima / Saran, Shweta

2024 Volume 116, Issue 5, Page(s) e2300067

Abstract: Background information: Two pore channels (TPCs) are voltage-gated ion channel superfamily members that release Ca: Results: We showed TPC2 protein localizes in lysosome-like acidic vesicles and the in situ data showed stalk cell biasness. Deletion ... ...

Abstract	Background information: Two pore channels (TPCs) are voltage-gated ion channel superfamily members that release Ca Results: We showed TPC2 protein localizes in lysosome-like acidic vesicles and the in situ data showed stalk cell biasness. Deletion of tpc2 showed defective and delayed development with formation of multi-tipped structures attached to a common base, while tpc2 Conclusion: TPC2 is required for effective development and differentiation in Dictyostelium and supports autophagic cell death and cell-type patterning. Significance: Decreased calcium due to deletion of tpc2 inhibit autophagic flux.
MeSH term(s)	Dictyostelium/genetics ; Dictyostelium/metabolism ; Dictyostelium/cytology ; Dictyostelium/growth & development ; Autophagy ; Protozoan Proteins/metabolism ; Protozoan Proteins/genetics ; Gene Deletion ; Calcium Channels/metabolism ; Calcium Channels/genetics ; Calcium/metabolism ; Cell Differentiation
Chemical Substances	Protozoan Proteins ; Calcium Channels ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2024-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	245745-3
ISSN	1768-322X ; 0399-0311 ; 0248-4900
ISSN (online)	1768-322X
ISSN	0399-0311 ; 0248-4900
DOI	10.1111/boc.202300067
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Article ; Online: Imidazo[1,2-a]pyridine based small organic fluorescent molecules for selective detection of nerve agents simulants.

Thakur, Ashima / Sharma, Abha

Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy

2022 Volume 282, Page(s) 121633

Abstract: A fused heterocyclic ESIPT imidazo[1,2-a]pyridine-based probes for colorimetric and fluorometric detection of nerve agents simulant sarin (DCP) and tabun (DCNP) are reported. The probes (5b, 6a & 6b) were found to be highly sensitive and selective for ... ...

Abstract	A fused heterocyclic ESIPT imidazo[1,2-a]pyridine-based probes for colorimetric and fluorometric detection of nerve agents simulant sarin (DCP) and tabun (DCNP) are reported. The probes (5b, 6a & 6b) were found to be highly sensitive and selective for the detection of DCNP and DCP at a micromolar concentration within seconds with no observed interference from other various types of analytes. The LOD for 6b towards DCP was found to be 0.6 µM with a linear range from 0 to 8 µM. The low-cost portable cellulose paper strip fabricated with probe 6b for real-time detection of DCP in the gas phase and spiked water has been developed. The paper strip product was found effective in detecting the presence of DCP in water and vapor state with substantial color changes which could be easily observed by the naked eye and under a handheld UV lamp at a wavelength of 365 nm.
MeSH term(s)	Colorimetry ; Fluorescent Dyes/analysis ; Nerve Agents/analysis ; Pyridines ; Water
Chemical Substances	Fluorescent Dyes ; Nerve Agents ; Pyridines ; Water (059QF0KO0R)
Language	English
Publishing date	2022-07-16
Publishing country	England
Document type	Journal Article
ZDB-ID	210413-1
ISSN	1873-3557 ; 0370-8322 ; 0584-8539 ; 1386-1425
ISSN (online)	1873-3557
ISSN	0370-8322 ; 0584-8539 ; 1386-1425
DOI	10.1016/j.saa.2022.121633
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Article ; Online: Alpha Lipoic Acid and Monoisoamyl-DMSA Combined Treatment Ameliorates Copper-Induced Neurobehavioral Deficits, Oxidative Stress, and Inflammation.

Patwa, Jayant / Thakur, Ashima / Flora, Swaran Jeet Singh

Toxics

2022 Volume 10, Issue 12

Abstract: Copper (Cu), being an essential trace metal, plays several roles in biological processes, though exposure to Cu can be potentially toxic to the brain and a few other soft organs. In the present study, we investigated the effects of the combined ... ...

Abstract	Copper (Cu), being an essential trace metal, plays several roles in biological processes, though exposure to Cu can be potentially toxic to the brain and a few other soft organs. In the present study, we investigated the effects of the combined administration of monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), which is a new chelator, and alpha lipoic acid (ALA) and an antioxidant that is made naturally in the body and is also found in foods, against Cu-induced oxidative stress in rats. Rats were exposed to 20 mg/kg copper sulfate for 16 weeks once a day via the oral route. After 16 weeks of exposure, animals were divided into different sub-groups. Group I was divided into three subgroups: Group IA, control; Group IB, MiADMSA (75 mg/kg, oral); Group IC, ALA (75 mg/kg, oral), while Group II was divided into four subgroups: Group IIA, Cu pre-exposed; Group IIB, Cu+ MiADMSA; Group IIC, Cu+ ALA; Group IID, Cu+ ALA+ MiADMSA. Exposure to Cu led to significant neurobehavioral abnormalities; treatment with MiADMSA, and in particular MiADMSA + ALA, significantly ameliorated the neurobehavioral parameters and restored the memory deficits in rats. Oxidative stress variables (ROS, nitrite, TBARS, SOD, catalase) and inflammatory markers (TNF-α, and IL-1β), which were altered on Cu exposed rats, also responded favorably to ALA+ MiADMSA combined treatment. Thus, combined administration of MiADMSA and ALA might be a better treatment strategy than monotherapy with MiADMSA or ALA against Cu-induced neurotoxicity, particularly in reducing oxidative stress, neurobehavioral abnormalities, and inflammatory markers.
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics10120718
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Article ; Online: Synthesis, Molecular Docking, BSA, and

Thakur, Ashima / Patwa, Jayant / Sharma, Abha / Flora, Swaran Jeet Singh

Medicinal chemistry (Shariqah (United Arab Emirates))

2021 Volume 18, Issue 2, Page(s) 273–287

Abstract: Aim: To synthesize and evaluate the fused heterocyclic imidazo[1,2-a]pyridine based oxime as a reactivator against paraoxon inhibited acetylcholinesterase.: Background: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, ... ...

Abstract	Aim: To synthesize and evaluate the fused heterocyclic imidazo[1,2-a]pyridine based oxime as a reactivator against paraoxon inhibited acetylcholinesterase. Background: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, monocrotophos, and diazinon, which are commonly used in agriculture for enhancing agricultural productivity via killing crop-damaging pests. However, people may get exposed to OPs pesticides unintentionally/intentionally via ingestion, inhalation, or dermal. The current treatment regimen includes reactivator such as mono or bis-pyridinium oximes along with anticholinergic and anticonvulsant drugs that are recommended for the treatment of OP poisoning. Unfortunately, the drawback of the existing reactivator is the permanent charge present on the pyridinium, making them inefficient to cross the blood-brain barrier (BBB) and reactivate OP-inhibited central nervous system (CNS) acetylcholinesterase. Therefore, there is a need of a reactivator that could cross the BBB and reactivate the OP inhibited acetylcholinesterase. Objective: The objectives of the study were synthesis, molecular docking, BSA binding, and in-vitro estimation of oximes of various substituted imidazo [1,2-a]pyridine against paraoxon inhibited acetylcholinesterase. Methods: The reactivators were synthesized in three steps and characterized using various spectroscopic techniques. The molecular docking study was performed on 2WHP and 3ZLV PDB using the Glide-XP software. The acid dissociation constant (pKa) of oximes was calculated experimentally, and the drug-likeness properties of the oximes were calculated in silico using Molinspiration and Swiss ADME software. The binding of oximes with bovine serum albumin (BSA) was also investigated using a Fluorescence spectrophotometer. The reactivation potential of the oximes was determined by in vitro enzymatic assay. Results: The In-silico study inferred that the synthesized molecules fulfilled the parameters required for a successful CNS drug candidate. Furthermore, in-vitro enzymatic assay indicated reasonable reactivation potential of the oximes against paraoxon-inhibited AChE. The binding of oximes with bovine serum albumin (BSA) revealed that there was a static quenching of intrinsic fluorescence of BSA by the oxime. The binding constant value and number of binding sites were found to be 0.24 x 10 Conclusion: The results of the study concluded that this scaffold could be used for further designing of more efficient uncharged reactivators.
MeSH term(s)	Acetylcholinesterase ; Cholinesterase Reactivators/pharmacology ; Humans ; Imidazoles ; Molecular Docking Simulation ; Oximes/pharmacology ; Paraoxon/toxicity ; Pyridines ; Serum Albumin, Bovine
Chemical Substances	Cholinesterase Reactivators ; Imidazoles ; Oximes ; Pyridines ; imidazopyridine ; Serum Albumin, Bovine (27432CM55Q) ; Acetylcholinesterase (EC 3.1.1.7) ; Paraoxon (Q9CX8P80JW)
Language	English
Publishing date	2021-02-10
Publishing country	Netherlands
Document type	Journal Article
ISSN	1875-6638
ISSN (online)	1875-6638
DOI	10.2174/1573406417666210208223240
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Article ; Online: Organic-Molecule-Based Fluorescent Chemosensor for Nerve Agents and Organophosphorus Pesticides.

Gori, Muskan / Thakur, Ashima / Sharma, Abha / Flora, S J S

Topics in current chemistry (Cham)

2021 Volume 379, Issue 5, Page(s) 33

Abstract: Organophosphorus (OP) compounds are typically a broad class of compounds that possess various uses such as insecticides, pesticides, etc. One of the most evil utilizations of these compounds is as chemical warfare agents, which pose a greater threat than ...

Abstract	Organophosphorus (OP) compounds are typically a broad class of compounds that possess various uses such as insecticides, pesticides, etc. One of the most evil utilizations of these compounds is as chemical warfare agents, which pose a greater threat than biological weapons because of their ease of access. OP compounds are highly toxic compounds that cause irreversible inhibition of enzyme acetylcholinesterase, which is essential for hydrolysis of neurotransmitter acetylcholine, leading to series of neurological disorders and even death. Due to the extensive use of these organophosphorus compounds in agriculture, there is an increase in the environmental burden of these toxic chemicals, with severe environmental consequences. Hence, the rapid and sensitive, selective, real-time detection of OP compounds is very much required in terms of environmental protection, health, and survival. Several techniques have been developed over a few decades to easily detect them, but still, numerous challenges and problems remain to be solved. Major advancement has been observed in the development of sensors using the spectroscopic technique over recent years because of the advantages offered over other techniques, which we focus on in the presented review.
MeSH term(s)	Acetylcholinesterase/chemistry ; Acetylcholinesterase/metabolism ; Carbocyanines/chemistry ; Electron Transport ; Fluorescent Dyes/chemistry ; Humans ; Microscopy, Fluorescence ; Nerve Agents/chemistry ; Nerve Agents/metabolism ; Organophosphorus Compounds/chemistry ; Organophosphorus Compounds/metabolism ; Pesticides/chemistry ; Pesticides/metabolism ; Spectrometry, Fluorescence
Chemical Substances	Carbocyanines ; Fluorescent Dyes ; Nerve Agents ; Organophosphorus Compounds ; Pesticides ; Acetylcholinesterase (EC 3.1.1.7)
Language	English
Publishing date	2021-08-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2848485-X
ISSN	2364-8961 ; 2365-0869
ISSN (online)	2364-8961
ISSN	2365-0869
DOI	10.1007/s41061-021-00345-7
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Article ; Online: Synthesis and evaluation of small organic molecule as reactivator of organophosphorus inhibited acetylcholinesterase.

Thakur, Ashima / Patwa, Jayant / Pant, Suyash / Jeet Singh Flora, Swaran / Sharma, Abha

Drug and chemical toxicology

2022 Volume 47, Issue 1, Page(s) 26–41

Abstract: A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) ... ...

Abstract	A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) inhibited
MeSH term(s)	Cholinesterase Inhibitors/toxicity ; Cholinesterase Inhibitors/chemistry ; Paraoxon ; Cholinesterase Reactivators/pharmacology ; Cholinesterase Reactivators/chemistry ; Acetylcholinesterase/metabolism ; Molecular Docking Simulation ; Oximes/pharmacology ; Oximes/chemistry ; Organophosphorus Compounds/toxicity ; Malathion/analogs & derivatives ; Nitrophenols
Chemical Substances	Cholinesterase Inhibitors ; Paraoxon (Q9CX8P80JW) ; Cholinesterase Reactivators ; Acetylcholinesterase (EC 3.1.1.7) ; malaoxon (2439JYF84Q) ; 2,6-dichloro-4-nitrophenol (618-80-4) ; Oximes ; Organophosphorus Compounds ; Malathion (U5N7SU872W) ; Nitrophenols
Language	English
Publishing date	2022-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	548368-2
ISSN	1525-6014 ; 0148-0545
ISSN (online)	1525-6014
ISSN	0148-0545
DOI	10.1080/01480545.2022.2150210
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Article ; Online: Monoisoamyl DMSA reduced copper-induced neurotoxicity by lowering 8-OHdG level, amyloid beta and Tau protein expressions in Sprague-Dawley rats.

Patwa, Jayant / Thakur, Ashima / Sharma, Abha / Flora, S J S

Metallomics : integrated biometal science

2020 Volume 12, Issue 9, Page(s) 1428–1448

Abstract: Introduction: copper dyshomeostasis has long been linked with several neurodegenerative disorders. The binding of Cu with amyloid beta and other neuronal proteins in the brain leads to the generation of oxidative stress, which eventually causes ... ...

Abstract	Introduction: copper dyshomeostasis has long been linked with several neurodegenerative disorders. The binding of Cu with amyloid beta and other neuronal proteins in the brain leads to the generation of oxidative stress, which eventually causes neurotoxicity. Method: the present study was aimed at elucidating the efficacy of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) and d-penicillamine (DPA) (0.3 mEq kg-1, oral administration for 2 weeks) against Cu(ii)-induced (20 mg kg-1, oral administration for 16 weeks) neurotoxicity in Sprague-Dawley (SD) rats. Results: we observed that the MiADMSA treatment modulated the altered oxidative and nitrosative stress parameters, antioxidant enzymes, and acetylcholinesterase (AChE) activity. Significant improvements were noticed in the neurobehavioral parameters except for the memory parameter. We also observed moderate improvement of memory impairment in the rats treated with MiADMSA and DPA post Cu(ii) exposure, as assessed by a passive avoidance test. Disease progression involves multiple factors and results in the up-regulation of intra and extracellular proteins such as amyloid beta and tau proteins; the expressions of these proteins were significantly reduced by the treatment proposed in our study, and these results were confirmed by ELISA and qRT-PCR. The expression of caspase-3 was higher in Cu(ii)-exposed rats, whereas it was lower in the MiADMSA-treated group. The proposed treatment reduced the copper-induced histological changes in the cortex and hippocampus regions of the brain. Conclusion: it can be summarised from the present study that MiADMSA is effective in reducing Cu(ii)-induced oxido-nitrosative stress, antioxidant defense enzymes, neurobehavioral changes, neuronal markers, apoptotic markers, and their genetic expressions. We conclude that chelation therapy using MiADMSA might be a promising approach for the treatment of copper-induced neurotoxicity.
MeSH term(s)	8-Hydroxy-2'-Deoxyguanosine/analysis ; Amyloid beta-Peptides/analysis ; Animals ; Brain/drug effects ; Brain Chemistry/drug effects ; Copper/adverse effects ; Male ; Molecular Docking Simulation ; Neuroprotective Agents/pharmacology ; Rats, Sprague-Dawley ; Succimer/analogs & derivatives ; Succimer/pharmacology ; tau Proteins/analysis
Chemical Substances	Amyloid beta-Peptides ; Neuroprotective Agents ; tau Proteins ; Copper (789U1901C5) ; 8-Hydroxy-2'-Deoxyguanosine (88847-89-6) ; monoisoamyl-2,3-dimercaptosuccinate (9O8B0VBE22) ; Succimer (DX1U2629QE)
Language	English
Publishing date	2020-07-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2474317-3
ISSN	1756-591X ; 1756-5901
ISSN (online)	1756-591X
ISSN	1756-5901
DOI	10.1039/d0mt00083c
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Article ; Online: Interaction study of monoisoamyl dimercaptosuccinic acid with bovine serum albumin using biophysical and molecular docking approaches.

Thakur, Ashima / Patwa, Jayant / Pant, Suyash / Sharma, Abha / Flora, S J S

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4068

Abstract: Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its ... ...

Abstract	Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its mechanism of interaction with bovine serum albumin protein (BSA). Therefore, the interaction between MiADMSA with BSA was investigated using various spectroscopic techniques and computational methods. Linear quenching of BSA intrinsic fluorescence intensity with the increasing concentration of MiADMSA was observed in the fluorescence study. Furthermore, synchronous results revealed that MiADMSA slightly changed the conformation of BSA. The binding constant value of the BSA-MiADMSA complex was found 1.60 × 10
MeSH term(s)	Binding Sites ; Circular Dichroism ; Fluorescence ; Molecular Docking Simulation/methods ; Protein Structure, Tertiary ; Serum Albumin, Bovine/chemistry ; Serum Albumin, Bovine/metabolism ; Spectroscopy, Fourier Transform Infrared ; Succimer/analogs & derivatives ; Succimer/chemistry ; Succimer/metabolism
Chemical Substances	Serum Albumin, Bovine (27432CM55Q) ; monoisoamyl-2,3-dimercaptosuccinate (9O8B0VBE22) ; Succimer (DX1U2629QE)
Language	English
Publishing date	2021-02-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-83534-0
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Article: Unravelling the therapeutic potential of orchid plant against cancer

Shukla, Monu Kumar / Monika / Thakur, Ashima / Verma, Rachna / Lalhlenmawia, H. / Bhattacharyya, Sanjib / Bisht, Dheeraj / Singh, Anita / Parcha, Versha / Kumar, Deepak

SAAB South African journal of botany. 2022 Nov., v. 150

2022

Abstract: Cancer is one of the deadly diseases all over the world which is defined as unregulated growth and division of the cells. Natural remedies, particularly derived from plants, were used to treat a range of illnesses for thousands of years, including cancer. ...

Abstract	Cancer is one of the deadly diseases all over the world which is defined as unregulated growth and division of the cells. Natural remedies, particularly derived from plants, were used to treat a range of illnesses for thousands of years, including cancer. Several orchid species have been reported as a cure to treat various types of cancers. Orchids are huge family of flower bearing plants. They are traditionally used in folk medicine for the cure of various infectious diseases and tumour. Many of bioactive compounds isolated from orchid plants such as Dendrobium longicornu Lindl., Dendrobium transparens, Rhyncostylish retusa, Vanda cristata, Anoectochilus formosanus etc. possess anticancer activities via modifying the biotransformation of potential carcinogens by xenobiotic-metabolizing enzymes, alteration of hormone synthesis, inhibition of cancer cell proliferation, suppression of protein expression, impede of cell cycle and impairment of cell growth. In actual circumstances active constituents present in orchidaceae family are not so explored. So, in this review we covered the article published till 2022 using different electronic databases PubMed/ MEDLINE, Scopus, Web of Science, and Google Scholar. The present review highlights the orchid plant family and its bioactive constituents with anticancer activity via various signalling pathways, as well as their possible mechanisms of action.
Keywords	Anoectochilus formosanus ; Dendrobium ; Vanda ; antineoplastic activity ; biotransformation ; cell cycle ; cell growth ; cell proliferation ; flowers ; neoplasm cells ; neoplasms ; protein synthesis ; therapeutics ; traditional medicine
Language	English
Dates of publication	2022-11
Size	p. 69-79.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2126918-X
ISSN	0254-6299
ISSN	0254-6299
DOI	10.1016/j.sajb.2022.07.005
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Article ; Online: Natural products and their derivatives as multifunctional ligands against Alzheimer's disease.

Patil, Pooja / Thakur, Ashima / Sharma, Abha / Flora, Swaran Jeet Singh

Drug development research

2019 Volume 81, Issue 2, Page(s) 165–183

Abstract: Alzheimer's disease (AD), a complex neurodegenerative disorder causing multiple cellular changes including impaired cholinergic system, beta-amyloid (βA) aggregation, tau hyperphosphorylation, metal dyshomeostasis, neuroinflammation, and many other ... ...

Abstract	Alzheimer's disease (AD), a complex neurodegenerative disorder causing multiple cellular changes including impaired cholinergic system, beta-amyloid (βA) aggregation, tau hyperphosphorylation, metal dyshomeostasis, neuroinflammation, and many other pathways are involved in the pathogenesis of the disease. However, the exact cause of the disease is not known. Natural products such as flavonoids, alkaloids, resveratrol, and curcumin have multifunctional properties, and have drawn the attention of the researchers because these molecules are capable of interacting concurrently with the multiple targets of AD. Therefore, natural products and their derivatives with proven efficacy could be used in the management of the neurodegenerative disorders. This review focuses on the natural product based multitarget directed ligands like tacrine-coumarin, tacrine-huperzine A, harmine-isoxazoline, berberine-thiophenyl, galantamine-indole, pyridoxine-resveratrol, donepezil-curcumin and their mode of action.
Language	English
Publishing date	2019-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604587-x
ISSN	1098-2299 ; 0272-4391
ISSN (online)	1098-2299
ISSN	0272-4391
DOI	10.1002/ddr.21587
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