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  1. Article ; Online: Recent advances in natural products targeting α-synuclein aggregation or clearance in Parkinson's disease

    Jay Gupta / Koneni V. Sashidhara

    European Journal of Medicinal Chemistry Reports, Vol 9, Iss , Pp 100114- (2023)

    2023  

    Abstract: Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of misfolded α-synuclein fibrils, leading to the formation of Lewy bodies. Currently, no effective treatment exists to halt the progression of the disease. Only ... ...

    Abstract Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of misfolded α-synuclein fibrils, leading to the formation of Lewy bodies. Currently, no effective treatment exists to halt the progression of the disease. Only symptomatic relief and dopamine replacement therapy are available, but they are unable to halt the underlying disease process. Therefore, there is an urgent need for targeted drugs that can effectively stop the progression of Parkinson's disease by specifically targeting the aggregation and clearance of α-synuclein through various mechanisms. In this context, natural products have emerged as a promising source of potential therapeutic agents. A significant number of drugs used in the treatment of central nervous system diseases are either natural products or derived from them. In this review, we focus on natural products discovered from 2015 onwards that target the aggregation and/or clearance of α-synuclein using diverse approaches. By exploring these natural compounds, we aim to shed light on their potential as therapeutic interventions for Parkinson's disease.
    Keywords Parkinson's disease ; Neurodegenerative disorder ; α-Synuclein ; Amyloid fibrils ; Inhibitors ; Natural products ; Pharmacy and materia medica ; RS1-441 ; Other systems of medicine ; RZ201-999
    Subject code 630
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Silver-catalyzed decarboxylative cyclization for the synthesis of substituted pyrazoles from 1,2-diaza-1,3-dienes and α-keto acids.

    Katiyar, Sarita / Kumar, Abhishek / Sashidhara, Koneni V

    Chemical communications (Cambridge, England)

    2022  Volume 58, Issue 52, Page(s) 7297–7300

    Abstract: A silver-catalyzed decarboxylative cyclization process has been developed for the synthesis of substituted pyrazoles from the readily available 1,2-diaza-1,3-dienes and α-keto acids. Under the optimized conditions, a series of multisubstituted pyrazoles ... ...

    Abstract A silver-catalyzed decarboxylative cyclization process has been developed for the synthesis of substituted pyrazoles from the readily available 1,2-diaza-1,3-dienes and α-keto acids. Under the optimized conditions, a series of multisubstituted pyrazoles were well prepared in moderate to good yields. In addition, the synthetic utility of this protocol has been demonstrated by synthesizing analogs of FDA approved drugs such as anti-inflammatory drug, lonazolac and antiobesity drug, rimonabant.
    MeSH term(s) Catalysis ; Cyclization ; Keto Acids ; Molecular Structure ; Polyenes ; Pyrazoles ; Silver
    Chemical Substances Keto Acids ; Polyenes ; Pyrazoles ; Silver (3M4G523W1G)
    Language English
    Publishing date 2022-06-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d2cc01793h
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  3. Article ; Online: Synergy between human DNA ligase I and topoisomerase 1 unveils new therapeutic strategy for the management of colorectal cancer.

    Maurya, Pooja / Rawat, Rohit Singh / Gupta, Sampa / Krishna, Shagun / Siddiqi, Mohammad Imran / Sashidhara, Koneni V / Banerjee, Dibyendu

    Journal of biomolecular structure & dynamics

    2024  , Page(s) 1–16

    Abstract: DNA topoisomerase 1 (Topo 1) is a pivotal player in various DNA processes, including replication, repair, and transcription. It serves as a target for anticancer drugs like camptothecin and its derivatives (Topotecan and SN-38/Irinotecan). However, the ... ...

    Abstract DNA topoisomerase 1 (Topo 1) is a pivotal player in various DNA processes, including replication, repair, and transcription. It serves as a target for anticancer drugs like camptothecin and its derivatives (Topotecan and SN-38/Irinotecan). However, the emergence of drug resistance and the associated adverse effects, such as alopecia, anemia, dyspnea, fever, chills, and painful or difficult urination, pose significant challenges in Topo 1-targeted therapy, necessitating urgent attention. Human DNA Ligase 1 (hLig I), recognized primarily for its role in DNA replication and repair of DNA breaks, intriguingly exhibits a DNA relaxation activity akin to Topo 1. This raised the hypothesis that hLig I might compensate for Topo 1 inhibition, contributing to resistance against Topo 1 inhibitors. To explore this hypothesis, we assessed the efficacy of hLig I inhibition alone and in combination with Topo 1 in cancer cells. As anticipated, the overexpression of hLig I was observed after Topo 1 inhibition in colorectal cancer cells, affirming our hypothesis. Previously identified as an inhibitor of hLig I's DNA relaxation activity, compound 27 (C 27), when combined with Topotecan, demonstrated a synergistic antiproliferative effect on colorectal cancer cells. Notably, cells with downregulated hLig I (
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2023.2297817
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  4. Article: Silver-catalyzed decarboxylative cyclization for the synthesis of substituted pyrazoles from 1,2-diaza-1,3-dienes and α-keto acids

    Katiyar, Sarita / Kumar, Abhishek / Sashidhara, Koneni V.

    Chemical communications. 2022 June 28, v. 58, no. 52

    2022  

    Abstract: A silver-catalyzed decarboxylative cyclization process has been developed for the synthesis of substituted pyrazoles from the readily available 1,2-diaza-1,3-dienes and α-keto acids. Under the optimized conditions, a series of multisubstituted pyrazoles ... ...

    Abstract A silver-catalyzed decarboxylative cyclization process has been developed for the synthesis of substituted pyrazoles from the readily available 1,2-diaza-1,3-dienes and α-keto acids. Under the optimized conditions, a series of multisubstituted pyrazoles were well prepared in moderate to good yields. In addition, the synthetic utility of this protocol has been demonstrated by synthesizing analogs of FDA approved drugs such as anti-inflammatory drug, lonazolac and antiobesity drug, rimonabant.
    Keywords acids ; chemical communication ; pyrazoles
    Language English
    Dates of publication 2022-0628
    Size p. 7297-7300.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d2cc01793h
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  5. Article ; Online: Antiglycation activity of

    Ahmad, Shadab / Pandey, Alka Raj / Singh, Suriya Pratap / Singh, Sushmita / Sashidhara, Koneni V / Tamrakar, Akhilesh K

    Natural product research

    2022  Volume 36, Issue 24, Page(s) 6329–6335

    Abstract: The increased formation and accumulation of advanced glycation end products (AGEs) has been implicated in pathogenesis of various chronic ailments, including diabetes-associated secondary complications, atherosclerosis, aging, inflammatory and ... ...

    Abstract The increased formation and accumulation of advanced glycation end products (AGEs) has been implicated in pathogenesis of various chronic ailments, including diabetes-associated secondary complications, atherosclerosis, aging, inflammatory and neurodegenerative diseases. Therefore, inhibition of AGEs formation is an imperative strategy for alleviating diverse pathologies. Here, we have demonstrated the AGEs inhibitory activity of
    MeSH term(s) Glycation End Products, Advanced ; Glycosylation ; Hydrolyzable Tannins ; Serum Albumin, Bovine/metabolism ; Fructose
    Chemical Substances glucogallin (58511-73-2) ; Glycation End Products, Advanced ; Hydrolyzable Tannins ; Serum Albumin, Bovine (27432CM55Q) ; Fructose (30237-26-4)
    Language English
    Publishing date 2022-01-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2185747-7
    ISSN 1478-6427 ; 1478-6419
    ISSN (online) 1478-6427
    ISSN 1478-6419
    DOI 10.1080/14786419.2022.2025799
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  6. Article ; Online: 16-Hydroxy-ent-halima-5(10),13-dien-15,16-olide from Polyalthia longifolia targets adipogenesis by inhibiting mitotic clonal expansion and ameliorates dyslipidemia.

    Khandelwal, Nilesh / Pandey, Alka Raj / Singh, Suriya Pratap / Rai, Prashant / Gupta, Sanchita / Kushwaha, Vinita / Singh, Astha / Gaikwad, Anil Nilkanth / Sashidhara, Koneni V

    Fitoterapia

    2023  Volume 170, Page(s) 105626

    Abstract: Obesity-related metabolic disorders are increasing at an alarming rate worldwide. The FDA has approved many molecules for weight loss therapy; most of them act on the gut level by inhibiting lipid uptake or on the central nervous system by controlling ... ...

    Abstract Obesity-related metabolic disorders are increasing at an alarming rate worldwide. The FDA has approved many molecules for weight loss therapy; most of them act on the gut level by inhibiting lipid uptake or on the central nervous system by controlling appetite. Limitations and drawbacks have propelled the search for new pharmacophores exhibiting favourable metabolic alteration at adipocytes, and natural products have always been there to prove their worth. In our efforts, we have identified 16-hydroxy-ent-halima-5(10),13-dien-15,16-olide (PLH), a halimane diterpene isolated from Polyalthia longifolia, demonstrating anti-adipogenic and anti-dyslipidemic activity. It inhibited adipogenesis in 3T3-L1 preadipocyte and C3H10T1/2 mesenchymal stem cell lines. Furthermore, it decreased set of adipogenic markers at transcript and protein levels. Cell cycle studies indicated that PLH halts the mitotic clonal expansion. Mechanistic studies shows that PLH activate Wnt/β-catenin signaling pathway to inhibit the adipogenesis. The study suggested that PLH inhibited adipogenesis during the early phase of differentiation by targeting mitotic clonal expansion and arresting the cell cycle in the G1 phase of the cell cycle. It improved the dyslipidemic condition in HFD-fed hamsters by decreasing the body weight, fat mass, eWAT weight and improving the serum lipid profile. Overall, PLH has been found as a potential drug candidate and a pharmacophore for combating metabolic disorders including obesity and dyslipidemia.
    MeSH term(s) Cricetinae ; Animals ; Humans ; Mice ; Adipogenesis ; Polyalthia ; Molecular Structure ; Cell Differentiation ; Obesity/drug therapy ; Dyslipidemias/drug therapy ; Lipids ; 3T3-L1 Cells
    Chemical Substances Lipids
    Language English
    Publishing date 2023-07-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 412385-2
    ISSN 1873-6971 ; 0367-326X
    ISSN (online) 1873-6971
    ISSN 0367-326X
    DOI 10.1016/j.fitote.2023.105626
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  7. Article ; Online: Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling.

    Tripathi, Ashish Kumar / Rai, Divya / Kothari, Priyanka / Kushwaha, Pragati / Sashidhara, Koneni V / Trivedi, Ritu

    Apoptosis : an international journal on programmed cell death

    2022  Volume 27, Issue 1-2, Page(s) 90–111

    Abstract: Glucocorticoid induced osteoporosis (GIOP) is the second most leading cause of osteoporosis. We have identified a compound, a benzofuran pyran hybrid compound 4e that has osteogenic potential and we wanted to assess its efficacy in GIOP in male mice. We ... ...

    Abstract Glucocorticoid induced osteoporosis (GIOP) is the second most leading cause of osteoporosis. We have identified a compound, a benzofuran pyran hybrid compound 4e that has osteogenic potential and we wanted to assess its efficacy in GIOP in male mice. We assessed the effect of dexamethasone and compound 4e on primary osteoblasts using various cell based and immunofluorescence assays. For in vivo studies we administered methylprednisolone and compound 4e as a prophylactic measure in male Balb/c mice for 28 days and then evaluated the effect on bone microarchitecture by microCT, bone formation by histology along with clinically relevant bone markers. Compound 4e preserved osteoblast differentiation as evident by higher ALP positive cells and mineralization in compound treated groups. Compound 4e also increased the expression of osteogenic genes. This compound guarded β-catenin expression both in vitro and in vivo as confirmed by western blot and immunofluorescence assays. This led to the preservation of bone microarchitecture and cortical thickness at 2.5 mg kg
    MeSH term(s) Animals ; Apoptosis ; Benzofurans/pharmacology ; Cell Differentiation ; Glucocorticoids/metabolism ; Male ; Mice ; Osteoblasts ; Osteogenesis ; Osteoporosis/chemically induced ; Osteoporosis/diagnostic imaging ; Osteoporosis/drug therapy ; Pyrans/pharmacology ; Wnt Signaling Pathway ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances Benzofurans ; Glucocorticoids ; Pyrans ; beta Catenin
    Language English
    Publishing date 2022-02-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1452360-7
    ISSN 1573-675X ; 1360-8185
    ISSN (online) 1573-675X
    ISSN 1360-8185
    DOI 10.1007/s10495-021-01702-z
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  8. Article ; Online: Lipid lowering agents of natural origin: An account of some promising chemotypes.

    Singh, Suriya P / Sashidhara, Koneni V

    European journal of medicinal chemistry

    2017  Volume 140, Page(s) 331–348

    Abstract: The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no ... ...

    Abstract The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting naturally occurring compounds and their derivatives as potential hypolipidemic agents. Some of the interesting natural chemotypes that can control the increased levels of plasma lipids and discussed in this review are compactin, lovastatin, gugglesterone, berberine, lupeol, phytol, polyprenol, aegeline, 4-hydroxyisoleucine, α-asarone, resveratrol, esculeoside A, swertiamarin, rutin, saucerneol B, curcumin and a clerodane diterpene.
    Language English
    Publishing date 2017-11-10
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2017.09.020
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  9. Article ; Online: Antileishmanial evaluation of triazole-butenolide conjugates: design, synthesis,

    Pandey, Alka Raj / Singh, Suriya Pratap / Ramalingam, Karthik / Yadav, Kanchan / Bisen, Amol Chhatrapati / Bhatta, Rabi Sankar / Srivastava, Mrigank / Tripathi, Renu / Goyal, Neena / Sashidhara, Koneni V

    RSC medicinal chemistry

    2023  Volume 14, Issue 6, Page(s) 1131–1142

    Abstract: In the quest to discover novel scaffolds with leishmanicidal effects, a series of 23 compounds containing the most promising 1,2,3-triazole and highly potent butenolide in one framework were synthesized. The synthesized conjugates were screened ... ...

    Abstract In the quest to discover novel scaffolds with leishmanicidal effects, a series of 23 compounds containing the most promising 1,2,3-triazole and highly potent butenolide in one framework were synthesized. The synthesized conjugates were screened against
    Language English
    Publishing date 2023-04-06
    Publishing country England
    Document type Journal Article
    ISSN 2632-8682
    ISSN (online) 2632-8682
    DOI 10.1039/d2md00464j
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  10. Article ; Online: Preclinical pharmacokinetic exploration of a novel osteoporotic quinazolinone-benzopyran-indole hybrid (S019-0385) using LC-MS/MS.

    Kumar, Mukesh / Chauhan, Mridula / Verma, Sarvesh Kumar / Biswas, Arpon / Ansari, Alisha / Mishra, Anjali / Sanap, Sachin Nashik / Bisen, Amol Chhatrapati / Sashidhara, Koneni V / Bhatta, Rabi Sankar

    Xenobiotica; the fate of foreign compounds in biological systems

    2023  Volume 53, Issue 6-7, Page(s) 484–497

    Abstract: 1. The current investigation was to develop and validate the LC-MS/MS method in order to analyse the various pharmacokinetic parameters of S019-0385. A sensitive, selective, and robust LC-MS/MS approach was established and validated for measuring S019- ... ...

    Abstract 1. The current investigation was to develop and validate the LC-MS/MS method in order to analyse the various pharmacokinetic parameters of S019-0385. A sensitive, selective, and robust LC-MS/MS approach was established and validated for measuring S019-0385 in female mice plasma and tissue, using optimal multiple reaction monitoring (MRM) transition
    MeSH term(s) Humans ; Mice ; Female ; Animals ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Tissue Distribution ; Biological Availability ; Feces ; Reproducibility of Results
    Language English
    Publishing date 2023-11-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 120287-x
    ISSN 1366-5928 ; 0049-8254
    ISSN (online) 1366-5928
    ISSN 0049-8254
    DOI 10.1080/00498254.2023.2265475
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