Browsing by Author "Sushil K. Singh"

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Alkaloids of zephyranthes flava
(1986) Shibnath Ghosal; Sushil K. Singh; Radhey S. Srivastava
From fresh, mature seeds of Zephyranthes flava, two new 2-oxyphenanthridinium alkaloids, zefbetaine and zeflabetaine along with 15 known free and glucosyloxy alkaloids have been isolated by gradient solvent extraction, chromatography and derivatization. The new compounds have been characterized by comprehensive spectroscopic analyses, chemical transformations and synthesis. Additionally, changes in the major alkaloids during development of the fruits have been analysed and their biological significance appraised. © 1986.
Anti‐ulcerogenic activity of fulvic acids and 4′‐methoxy‐6‐carbomethoxybiphenyl isolated from shilajit
(1988) Shibnath Ghosal; Sushil K. Singh; Yatendra Kumar; Radheyshyam Srivastava; Raj K. Goel; Radharaman Dey; Salil K. Bhattacharya
Fulvic acids (FA) and 4′‐methoxy‐6‐carbomethoxybiphenyl (MCB, 1), two major organic compounds isolated from Shilajit (a humus product), were screened for anti‐ulcerogenic activity in albino rats. Both FA and MCB showed significant anti‐ulerogenic effects in the battery of tests accepted for this purpose. The mechanism of anti‐ulcerogenic action was studied with MCB on the basis of its effects on mucin content (gastric juice carbohydrates and carbohydrate/protein ratio) and on the concentration of DNA and protein in the gastric juice. The MCB‐induced changes in the mucosa provided resistance against the effect of ulcerogens and also against shedding of mucosal cells. A preliminary acute toxicity study indicated that both FA and MCB had a low order of toxicity. Copyright © 1988 John Wiley & Sons, Ltd.
Assessment of in vitro antipsoriatic activity of selected Indian medicinal plants
(Taylor and Francis Ltd, 2015) Sushil K. Singh; Hemendra S. Chouhan; Alekh N. Sahu; Gopeshwar Narayan
Context: Phyllanthus simplex Retz. (Phyllanthaceae), Crotolaria juncea Linn. (Leguminosae), Leucas aspera Linn. (Lamiaceae), and Vitex glabrata R.Br. (Verbenaceae) are well-known Indian medicinal plants. Different parts of these plants are used for healing purposes traditionally in the treatment of psoriasis and various other disorders. This prompted us to assess the antipsoriatic activities of these plants. Objectives: Petroleum ether and ethanol extracts of the selected plants, i.e., P. simplex (whole plant), C. juncea (seeds), L. aspera (aerial parts), and V. glabrata (leaves) were investigated for their in vitro antipsoriatic activity. Materials and methods: Antipsoriatic activity of the extracts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, using HaCaT cells. About 200μl of different concentrations (25, 50, 100, 200, and 400μg/ml) of test samples were prepared in the cell culture medium and incubated for 24h before MTT assay to determine the viable cells. The effect of these extracts on nitric oxide (NO) production and lipid peroxidation was also evaluated. Results: Our findings revealed that these plants showed promising skin keratinocyte antiproliferative activity. However, the petroleum ether extract of C. juncea (CJPE) and ethanol extract of L. aspera (LAEE) were found to exhibit significant activity (IC50 value=45.45 and 55.36μg/ml, respectively). Discussion and conclusions: The inhibitory action against NO production and lipid peroxidation in HaCaT cells suggested that the antipsoriatic activity of the extracts was mediated by an antioxidant mechanism. These findings validate the claims of the use of these plants in the treatment of psoriasis. © 2015 © 2015 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.
Benzothiazole derivatives bearing amide moiety: Potential cytotoxic and apoptosis-inducing agents against cervical cancer
(Lippincott Williams and Wilkins, 2016) Meenakshi Singh; Arusha Modi; Gopeshwar Narayan; Sushil K. Singh
Cervical cancer is a major cause of morbidity and mortality in women worldwide. In recent years, benzothiazole analogues have attracted considerable attention in anticancer research. Therefore, in this study, the earlier reported amide series of benzothiazole derivatives were investigated for their antiproliferative activity. The activity of amide derivatives was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometric analysis, apoptosis assay, and DNA fragmentation on two human cervical cancer cell lines: SiHa and C33-A. The data reported from this investigation indicated that benzothiazole derivatives show pronounced cytotoxicity in the HPV16-positive SiHa cells compared with HPV-negative C-33A cells. The in-vitro cytotoxicity of the compounds on the HEK-293 noncancer cell line was evaluated to establish selectivity. Cells treated with benzothiazole derivatives showed prominent morphological features as evidenced by cell shrinkage, membrane blebbing, apoptotic nuclei, and DNA fragmentation. The benzothiazole derivatives show accumulation of cells in the sub-G1 and S-phase of the cell cycle in SiHa and C33-A, respectively. In addition, these derivatives exert their beneficial effect by inducing apoptosis, in the chemoprevention of cervical cancer cells, and were further ascertained using a DNA fragmentation assay. The compounds studied showed potent cytotoxic and apoptotic properties against SiHa and C33-A cancer cell lines and thus represent an excellent starting point for further optimization of therapeutically effective anticancer drugs. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Design, synthesis and biological evaluation of carbazole derivatives as antitubercular and antibacterial agents
(Bentham Science Publishers B.V., 2019) Satheeshkumar Sellamuthu; Mohammad F. Bhat; Ashok Kumar; Gopal Nath; Sushil K. Singh
Background: The neuroleptic chlorpromazine has been reported for antitubercular activity but the associated antipsychotic activity restricted its clinical presentation. Objectives: Novel derivatives of carbazole having structural similarity with chlorpromazine were designed, in an attempt to reduce the associated side effects, while retaining the antitubercular activity. Materials and Methods: The designed molecules were synthesized and screened for antitubercular and antibacterial activities. The blood-brain barrier (BBB) permeability and mammalian cell (VERO) cytotoxicity (CC50) were examined to determine the safety of compounds. Results: Among the developed compounds, 14c, 15c, 16c and 17c were found to be promising against Mtb H37Rv at MIC of 1.56 μg/ml. They were also effective against S. aureus and E. coli at MIC of 0.98 and 7.81 μg/ml, respectively. The BBB permeability of the compounds was found to be less than chlorpromazine. Therefore, the developed compounds are expected to have diminished antipsychotic effect. The compounds were further marked safe against mammalian VERO cells at CC 50 > 90 μg/ml. Conclusion: The profound antitubercular activity with a concomitant reduction in BBB permeability of carbazole derivatives can pave new vista in the discovery of antitubercular drugs. © 2019 Bentham Science Publishers.
Design, synthesis and mode of action of novel 2-(4-aminophenyl)benzothiazole derivatives bearing semicarbazone and thiosemicarbazone moiety as potent antimicrobial agents
(Birkhauser Boston, 2016) Meenakshi Singh; Sudhir Kumar Singh; Mayank Gangwar; Gopal Nath; Sushil K. Singh
A novel series of substituted benzothiazoles, bearing semicarbazone and thiosemicarbazone moieties, was designed, synthesized and evaluated for their antimicrobial activity and possible mode of action. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, IR and Mass spectral data. The results revealed that compounds SC06, SC09, TS05 and TS07 have potent antibacterial activity against both Gram-positive and Gram-negative strains. Compound TS05 displayed most potent activity with MIC values of 3.91, 7.81 and 1.56 μg/ml against S. aureus, E. coli and P. aeruginosa, respectively. The results from cytoplasmic membrane permeabilization assay, FACS study as well as DNA-binding assays, evaluated against clinically relevant pathogens S. aureus and E. coli, suggest membrane perturbing as well as intracellular mode of action of this class of compounds. In addition, hemolytic activity of the compounds was measured which indicated their low cytotoxicity. © 2015 Springer Science+Business Media New York.
Design, synthesis and mode of action of some benzothiazole derivatives bearing an amide moiety as antibacterial agents
(Royal Society of Chemistry, 2014) Sushil K. Singh; Meenakshi Singh; Sudhir K. Singh; Mayank Gangwar; Gopal Nath
In this study ten benzothiazole derivatives bearing the amide moiety were designed, synthesized and evaluated for their antibacterial activity and possible mode of action. Structures of the synthesized compounds were elucidated by spectral data. Four different Gram-negative and two different Gram-positive bacterial strains were used in antibacterial activity tests. Among all the synthesised compounds, compound A07 displayed the most potent inhibitory activity with minimum inhibitory concentration (MIC) values of 15.6, 7.81, 15.6, 3.91 μg ml-1 against S. aureus, E. coli, S. typhi and K. pneumoniae respectively. Structure-activity relationship (SAR) studies revealed that electronic and lipophillic factors of the phenyl ring had a significant effect on the antimicrobial activity of the designed compounds. The benzothiazole bearing amide (A01-A10) series exhibited different modes of action based on aryl group substitution as revealed by studies on intact bacterial cells and plasmid DNA. The present study provides us two active compounds (A07 and A10) with a membrane perturbing mode of action, and an intracellular mode of action due to binding with DNA along with potent activity against clinically relevant pathogens E. coli and S. aureus. © 2014 the Partner Organisations.
Design, synthesis and mode of action of some new 2-(4'-aminophenyl) benzothiazole derivatives as potent antimicrobial agents
(Bentham Science Publishers B.V., 2016) Meenakshi Singh; Sudhir Kumar Singh; Mayank Gangwar; Satheeshkumar Sellamuthu; Gopal Nath; Sushil K. Singh
Background: The rapid evolution of antibiotic resistance poses a serious threat to public health. The development of heterocyclic benzothiazole derivatives, as efficient and potential agents, has been the focus of antibacterial drug discovery. Objective: Present study attempts to evaluate the antibacterial activity and mechanism of action of novel 2-(4'- aminophenyl) benzothiazole derivatives. Methods: Antibacterial activity of novel benzothiazole derivatives was evaluated by agar disc diffusion method against a panel of susceptible Gram-positive and Gram-negative strains. The mechanism of action was explored by bactericidal kinetics, membrane depolarization, fluorescent assisted cell cytometry and DNA cleavage studies. Results: Our findings revealed that compounds A07a and A07b turned out to be the most potent analogues having minimum inhibitory concentration values in the range of 3.91-31.2 g/ml against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli. The new benzothiazole derivatives displayed different modes of action as elucidated by the studies on intact bacterial cells and plasmid DNA. The structure activity relationship studies showed prominent activity of compound A07a containing oxime moiety on carbonyl carbon along with less bulky electron releasing and lipophillic group (methoxy and chloro) in phenyl ring at C2 position of 2-(4'-aminophenyl) benzothiazole ring system. Conclusion: The potent antibacterial activity of compounds (A07a and A07b) was mediated by membrane perturbing and intracellular mode of actions. These results further validate the use of these derivatives in the treatment of microbial diseases and provide scope for further research. © 2016 Bentham Science Publishers.
Development of Donor-Acceptor Architecture-Based Potential Theranostic Fluorescent Probes for Alzheimer’s Disease
(American Chemical Society, 2025) Nilesh Gajanan Bajad; T. A. Gajendra; Khushboo Sharma; Madhu Gwaldas Tapadia; Ashok Kumar; Sairam Krishnamurthy; Sushil K. Singh
The cholinergic deficits and deposition of β-amyloid (Aβ) species are regarded as the key events contributing to the progression of Alzheimer’s disease (AD). Herein, a series of novel donor-acceptor architecture-type potential theranostic agents were designed, synthesized, and evaluated for their potential against cholinesterase (ChE) enzymes and detection of Aβ species, which are primary targets in the development of therapeutics for AD. The optimal compound/probe 18 containing a benzothiazolium fluorophore with a bifunctional electron-donating N-aryl piperazine scaffold exhibited potent inhibitory activities against acetylcholinesterase (AChE; IC50 = 0.172 ± 0.011 μM) and butyrylcholinesterase (BuChE; IC50 = 1.376 ± 0.141 μM). Measurement of fluorescence properties showed that probe 18 exhibited emission maxima (λem) of >610 nm in dimethyl sulfoxide (DMSO) and >590 nm in PBS, suitable for the fluorescence imaging. In vitro studies demonstrated a change in fluorescence characteristics and high binding affinities (18; Kd = 0.731 μM) upon binding with Aβ aggregates. The affinity of probe 18 toward Aβ aggregates was further observed in elavGAL4 > UAS Aβ, the Drosophila larval brain sections, using a fluorescence imaging technique. The in vivo acute oral toxicity evaluation indicated a safety profile of the lead probe 18. Moreover, in vivo behavioral studies including Y-maze and novel object recognition tests signified that the administration of compound 18 improved cognitive and spatial memory impairment at a dose of 10 and 20 mg/kg in the scopolamine-induced cognitive deficit model. © 2025 American Chemical Society.
Dichotosin and dichotosinin, two adaptogenic glucosyloxy flavans from Hoppea dichotoma
(1985) Shibnath Ghosal; Dinesh K. Jaiswal; Sushil K. Singh; Radhey S. Srivastava
From the roots of Hoppea dichotoma, collected before flowering, two new naturally occurring glucosyloxyflavans, dichotosin and dichotosinin, have been isolated and characterized by means of comprehensive spectral analyses, chemical transformation and synthesis of the aglucone of dichotosin. This is the first report of dichotosinin from a natural source. Additionally, one known glucosyloxyflavan, diffutin, earlier reported in another Gentianaceae species (Canscora diffusa) also has now been isolated from this species. The glucosyloxyflavans, individually and in combination, produced varying degrees of adaptogenic (anti-stress-anti-anxiety) activity in animal models. This observation is consistent with the use of the plant extract as a nerve tonic in Ayurvedic medicine. © 1985.
Discovery of reversible selective monoamine oxidase B inhibitors with anti-acetylcholinesterase activity derived from 4-oxo-N-4-diphenyl butanamides
(Newlands Press Ltd, 2023) Srabanti Jana; Tania Nasreen; Sushil K. Singh
Aim: Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition. Materials & methods: With the help of fragment-based drug design, some 4-oxo-N-4-diphenyl butanamides were designed and synthesized as MAO-B inhibitors with anti-acetylcholinesterase (AChE) activity. Results: Compound 6m showed the best neuroprotection, with reversible selective MAO-B inhibition activity (IC50 = 11.54 ± 0.64 nM). Compounds 6b, 6h, 6j, 6n and 6p (IC50 = 20.90 ± 0.50, 17.25 ± 0.90, 15.85 ± 0.16, 16.81 ± 0.85 and 25.19 ± 0.17 nM, respectively) also appeared as potent and selective MAO-B inhibitors with anti-AChE activity. Conclusion: The present study suggests potent, neuroprotective and nontoxic lead compounds as selective MAO-B inhibitors with anti-AChE activity. © 2023 Newlands Press.
Effects of stress on alkaloid metabolism in Crinum asiaticum
(1990) Shibnath Ghosal; Sushil K. Singh; Sankara G. Unnikrishnan
The biochemical role of free and conjugated alkaloids in the fruits of Crinum asiaticum during strees (incisional injury and attack by an insect) is appraised. Wounding of C. asiaticum fruits caused almost complete hydrolysis of the alkaloidal conjugates and also produced oxidized metabolises of lycorine and its analogues. Prior treatment of fruits with anaesthetic agents, e.g. ether and lidocaine, not only protected the alkaloidal conjugates from hydrolysis but also prevented their oxidation. The qualitative and quantitative changes observed in the alkaloids, in response to the stress, suggest their role in protective and repair mechanisms of the producer plant, notably, augmentation of a 'second messenger', cAMP, in the fruits in response to injury and systemic administration of theophylline was observed. Prior administration of anaesthetic agents (ether or lidocaine), kept the concentration of cAMP significantly low despite inflicting subsequent injury. © 1990.
Flavans from Zephyranthes flava
(1985) Shibnath Ghosal; Sushil K. Singh; Radhey S. Srivastava
A new optically active flavan aglucone, 7-hydroxy-3′,4′-methylenedioxyflavan, and its 7-glucoside have been isolated from the bulbs of Zephyranthes flava, collected at flowering. Additionally, two known flavans, 7,4′-dihydroxy-3′-methoxyflavan and 7-methoxy-2′-hydroxy-4′,5′-methylenedioxyflavan, have been isolated for the first time from this species. The structures of these flavans have been established by comprehensive analyses (UV, IR, 1H NMR, 13C NMR, mass spectrometry, [α]D) of the compounds and their acetates, and also by chemical correlation. © 1985.
Free and glucosyloxy acetophenones from Pancratium biflorum
(1989) Shibnath Ghosal; Peeyush Mittal; Yatendra Kumar; Sushil K. Singh
Two new dimethoxy-acetophenone-O-glucosides and the known 2,4,6-trimethoxyacetophenone were isolated from the flowering bulbs and pseudo-stem fluid of Pancratium biflorum. The structures of the new compounds were established as 4,6-dimethoxyacetophenone-2-O-β-d-glucoside and 2,6-dimethoxyacetophenone-4-O-β-d-glucoside on the basis of chemical transformation, comprehensive spectroscopic analyses, and synthesis of the aglucones. The biological activity profile of the glucosides and their aglucones is also appraised. © 1983.
Isocraugsodine, an n-arylidenephenethylamine from Crinum asiaticum and its e-z isomerism
(1988) Shibnath Ghosal; Amirthalingam Shanthy; Sushil K. Singh
A new Schiff's base, named isocraugsodine, was isolated from the fruits of Crinum asiaticum. Its N-(3- methoxy-4-hydroxybenzylidene)- 4′-hydroxyphenethylamine structure was assigned on the basis of chemical trans- formation and comprehensive spectroscopic evidence. The temperature-gradient distribution of the three isomeric forms (1a⇌1b⇌1c) of the Schiff's base was determined by high resolution 1H NMR analysis. Isocraugsodine is considered as a direct precursor to Amaryllidaceae alkaloids. © 1988.
Mast cell protecting effects of shilajit and its constituents
(1989) Shibnath Ghosal; Jawahar Lal; Sushil K. Singh; Gautam Dasgupta; Joydeep Bhaduri; Mita Mukhopadhyay; Salil K. Bhattacharya
The effects of shilajit and the combined effects of its main constituents, fulvic acids (FAs), 4′‐methoxy‐6‐carbomethoxybiphenyl (MCB) and 3,8‐dihydroxy‐dibenzo‐α‐pyrone (DDP), were studied in relation to the degranulation and disruption of mast cells against noxious stimuli. Shilajit and different combinations of FAs, MCB and DDP provided statistically significant protection to antigen‐induced degranulation of sensitized mast cells, markedly inhibited the antigen‐induced spasm of sensitized guinea‐pig ileum, and prevented mast cell disruption induced by compound 48/80. The findings are appraised in view of the clinical use of shilajit in the treatment of allergic disorders in Ayurvedic medicine. Copyright © 1989 John Wiley & Sons, Ltd.
Occurrence of two epimeric alkaloids and metabolism compared with lycorine in Crinum latifolium
(1989) Shibnath Ghosal; Sankara Unnikrishnan; Sushil K. Singh
Two new epimeric pyrrolophenanthridine alkaloids, 2-epilyocorine and 2-epipancrassidine, were isolated from the flower-stem fluid of Crinum latifolium. The structures of the two alkaloids were established by spectroscopic analyses, crucial chemical transformation, and synthesis in case of the former. The differences in the metabolic pathways of lycorine and 2-epilycorine were studied under simulated physiological conditions and their biochemical significance was appraised. © 1989.
Parasitism of imperata cylindrica on pancratium biflorum and the concomitant chemical changes in the host species
(1986) Shibnath Ghosal; Yatendra Kumar; Dilip K. Chakrabarti; Jawahar Lal; Sushil K. Singh
A rare incidence of phanerogamic parasitism of Imperata cylindrica on Pancratium biflorum and the concomitant changes in the chemical constituents, from the hypersensitive responses in the host species, are reported. © 1986.
Phosphatidylpyrrolophenanthridine alkaloids from Zephyranthes flava
(1987) Shibnath Ghosal; Sushil K. Singh; Sankara G. Unnikrishnan
Four new alkaloidal phospholipids, 2-O-glycerophosphoryllycorine, phosphatidyllycorines, phosphatidylpseudolycorines and phosphatidyllycorinium methocation, were isolated from the flowers of Zephyranthes flava. The structures of these compounds were established by comprehensive spectral analyses, chemical transformations and synthesis, where possible. The biological profile of this novel group of alkaloidal conjugates is appraised. © 1987.
Preliminary studies on ligand-based design and evaluation of new mycobacterial ATP synthase inhibitors
(Bentham Science Publishers B.V., 2018) Satheeshkumar Sellamuthu; Amer H. Asseri; Hojjat Ghasemi Goojani; Gopal Nath; Sushil K. Singh
Background: Tuberculosis is a threat to humankind due to the development of resistance against the existing drugs, so new drugs are an absolute necessity. Neuroleptic phenothiazines were reported for antitubercular activity, but the associated antipsychotic effect restricted their antitubercular use. Objective: Novel mycobacterial ATP synthase inhibitors having structural similarity with phenothiazines were designed in an attempt to develop potent antitubercular agents with no or less side effects. Methods: The designed molecules were synthesized and screened against Mycobacterium tuberculosis H37Rv (Mtb). The compounds with strongest growth inhibition of whole Mtb (S3, S4, S9, S10, and S16) were screened for ATP synthesis inhibition using inverted membrane vesicles from Mycobacterium smegmatis, and were also screened for blood-brain barrier (BBB) permeability and mammalian cell cytotoxicity to assess the possible side effects. Results: Among all the compounds, S9 and S10 were found to be the most active (6.25 µg/mL) against Mtb and were comparable to chlorpromazine (12.5 µg/mL). Moreover, the compounds inhibited ATP synthesis at IC50 of 14 and 10.4 µM, respectively. A better correlation between MIC and IC50 observed, indicated that the compounds acted through mycobacterial ATP synthase inhibition. The blood-brain barrier (BBB) crossing ability of the compounds (S9, S10) was found to be less, indicating diminished CNS side effects. The compounds (S3, S4, S9, S10, and S16) were also marked safe against mammalian VERO cells, as CC50 was > 102 µg/mL. Conclusion: The enhanced antitubercular activity with reduced BBB permeability exhibited by the compounds has good prospect to develop them as antitubercular drugs. © 2018 Bentham Science Publishers.