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1.
Langmuir ; 40(19): 9855-9872, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38687994

ABSTRACT

Two-dimensional (2D) layered materials like graphene, transition-metal dichalcogenides (TMDs), boron nitrides, etc., exhibit unique and fascinating properties, such as high surface-to-volume ratio, inherent mechanical flexibility and robustness, tunable bandgap, and high carrier mobility, which makes them an apt candidate for flexible electronics with low consumption of power. Because of these properties, they are in tremendous demand for advancement in energy, environmental, and biomedical sectors developed through various technologies. The production and scalability of these materials must be sustainable and ecofriendly to utilize these unique properties in the real world. Here, in this current review, we review molybdenum disulfide (MoS2 nanosheets) in detail, focusing on exfoliated MoS2 in water and the applicability of aqueous MoS2 suspensions in various fields. The exfoliation of MoS2 results in the formation of single or few-layered MoS2. Therefore, this Review focuses on the few layers of exfoliated MoS2 that have the additional properties of 2D layered materials and higher excellent compatibility for integration than existing conventional Si tools. Hence, a few layers of exfoliated MoS2 are widely explored in biosensing, gas sensing, catalysis, photodetectors, energy storage devices, a light-emitting diode (LED), adsorption, etc. This review covers the numerous methodologies to exfoliate MoS2, focusing on the various published methodologies to obtain nanosheets of MoS2 from water solutions and their use.

2.
Future Med Chem ; 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37350114

ABSTRACT

Aim: To design a series of neoteric benzylidene amino-benzimidazole derivatives and to synthesize and evaluate them for anti-inflammatory and antioxidant potential. Methods: The designed target scaffolds were synthesized and appraised for in vitro antioxidant action and in vivo anti-inflammatory potential. AutoDock Vina software was employed for design; the Mannich reaction was used for synthesis; and antioxidant and anti-inflammatory potential were demonstrated by the 2,2-diphenyl-1-picryl hydrazyl free-radical scavenging assay and carrageenan-induced paw edema method, respectively. Results: Methyl-incorporating molecules 3-(2-((2-methylbenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one (6c) and 3-(2-((4-methylbenzylidene)amino-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one (6j) showed remarkable antioxidant and anti-inflammatory action, followed by compounds 6f, 6e and 6i containing 3-CH3, 2-OH, 4-F substituents, respectively. Conclusion: The designed analogs were dynamically confined within the active site of cyclooxygenase-2, and in vitro and in vivo results agreed with molecular docking studies.

3.
Indian J Psychol Med ; 45(3): 271-276, 2023 May.
Article in English | MEDLINE | ID: mdl-37152384

ABSTRACT

Background: Adolescence is a phase of many physical and psychological developments. This stage is also vulnerable to the development of mental illness. Anxiety is one of the most prevalent disorders among adolescents, which mostly onsets before puberty. This study aimed to understand the perception on anxiety among adolescents and mental health professionals and develop a comic strip on anxiety. Methods: This qualitative study involved focus group discussions (FGDs) among mental health professionals and pre-university college students. The FGD data were analyzed through direct content analysis according to the predetermined broad themes. Results: Awareness regarding anxiety was poor among adolescents, and in certain situations they were found to be reluctant to seek professional help. The comic strip on anxiety was developed based on the findings of FGD based on the themes, general awareness, factors responsible, symptoms and coping, management, and barriers to seeking professional help. Conclusions: Adolescents perceived mental health as very important for their overall health. The adolescents did not know that they were going through anxiety, but they noticed that they had some mental health issues and wanted to get out of it. The development of comic strip on anxiety for adolescents was an attempt to overcome these barriers.

4.
Small ; 19(31): e2206680, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36932892

ABSTRACT

Carbon dots are defined as small carbon nanoparticles with effective surface passivation via organic functionalization. The definition is literally a description of what carbon dots are originally found for the functionalized carbon nanoparticles displaying bright and colorful fluorescence emissions, mirroring those from similarly functionalized defects in carbon nanotubes. In literature more popular than classical carbon dots are the diverse variety of dot samples from "one-pot" carbonization of organic precursors. On the two different kinds of samples from the different synthetic approaches, namely, the classical carbon dots versus those from the carbonization method, highlighted in this article are their shared properties and apparent divergences, including also explorations of the relevant sample structural and mechanistic origins for the shared properties and divergences. Echoing the growing evidence and concerns in the carbon dots research community on the major presence of organic molecular dyes/chromophores in carbonization produced dot samples, demonstrated and discussed in this article are some representative cases of dominating spectroscopic interferences due to the organic dye contamination that have led to unfound claims and erroneous conclusions. Mitigation strategies to address the contamination issues, including especially the use of more vigorous processing conditions in the carbonization synthesis, are proposed and justified.

5.
Chem Biol Interact ; 373: 110379, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36738914

ABSTRACT

A novel series of pyrazolyl chalcones containing quinoline scaffold, 5 a-v has been synthesized by Claisen Schimdt condensation of aromatic acetophenone with 1-(4-methylquinolin-2-yl)-3-aryl-1H-pyrazole-4-carbaldehyde in quantitative yield. The compounds were characterized using IR, NMR, MS and elemental analysis. An E-configuration about CC ethylenic bond was determined using 1H NMR spectroscopy. These compounds exhibited significant antimalarial potential against CQ-sensitive and CQ-resistant strain of Plasmodium falciparum. Structure activity relationship has also been established based on outcomes of in vitro schizont inhibition assay. Compound 5u, (Z)-3-(1-(4-methylquinolin-2-yl)-3-p-tolyl-1H-pyrazol-4-yl)-1-p-tolylprop-2-en-1-one, was found to be the most potent among the series of synthetic analogues. In vivo, it demonstrated significant parasitemia suppression of 78.01% at a dose of 200 mg/kg against P. berghei in infected mice without any mortality in 7 days. In silico molecular docking study revealed that this compound 5u bound to the active site of cysteine protease falcipain-2 enzyme. Furthermore, in silico ADME studies, were also performed and physicochemical qualifications of the title compounds were determined. The biological outcomes of newer heterocyclic compounds may pave the new paths for researchers in development of potential antimalarial agents.


Subject(s)
Antimalarials , Chalcones , Quinolines , Mice , Animals , Antimalarials/pharmacology , Molecular Docking Simulation , Structure-Activity Relationship
6.
Cells ; 11(14)2022 07 12.
Article in English | MEDLINE | ID: mdl-35883618

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, positive sense, single stranded RNA (+ssRNA) virus, belonging to the genus Betacoronavirus and family Coronaviridae. It is primarily transmitted from infected persons to healthy ones through inhalation of virus-laden respiratory droplets. After an average incubation period of 2-14 days, the majority of infected individuals remain asymptomatic and/or mildly symptomatic, whereas the remaining individuals manifest a myriad of clinical symptoms, including fever, sore throat, dry cough, fatigue, chest pain, and breathlessness. SARS-CoV-2 exploits the angiotensin converting enzyme 2 (ACE-2) receptor for cellular invasion, and lungs are amongst the most adversely affected organs in the body. Thereupon, immune responses are elicited, which may devolve into a cytokine storm characterized by enhanced secretion of multitude of inflammatory cytokines/chemokines and growth factors, such as interleukin (IL)-2, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (GCSF), basic fibroblast growth factor 2 (bFGF2), monocyte chemotactic protein-1 (MCP1), interferon-inducible protein 10 (IP10), macrophage inflammatory protein 1A (MIP1A), platelet-derived growth factor subunit B (PDGFB), and vascular endothelial factor (VEGF)-A. The systemic persistence of inflammatory molecules causes widespread histological injury, leading to functional deterioration of the infected organ(s). Although multiple treatment modalities with varying effectiveness are being employed, nevertheless, there is no curative COVID-19 therapy available to date. In this regard, one plausible supportive therapeutic modality may involve administration of mesenchymal stem cells (MSCs) and/or MSC-derived bioactive factors-based secretome to critically ill COVID-19 patients with the intention of accomplishing better clinical outcome owing to their empirically established beneficial effects. MSCs are well established adult stem cells (ASCs) with respect to their immunomodulatory, anti-inflammatory, anti-oxidative, anti-apoptotic, pro-angiogenic, and pro-regenerative properties. The immunomodulatory capabilities of MSCs are not constitutive but rather are highly dependent on a holistic niche. Following intravenous infusion, MSCs are known to undergo considerable histological trapping in the lungs and, therefore, become well positioned to directly engage with lung infiltrating immune cells, and thereby mitigate excessive inflammation and reverse/regenerate damaged alveolar epithelial cells and associated tissue post SARS-CoV-2 infection. Considering the myriad of abovementioned biologically beneficial properties and emerging translational insights, MSCs may be used as potential supportive therapy to counteract cytokine storms and reduce disease severity, thereby facilitating speedy recovery and health restoration.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Adult , COVID-19/therapy , Cytokine Release Syndrome , Humans , Immunity , Immunomodulation , Mesenchymal Stem Cells/metabolism , SARS-CoV-2
7.
Chemosphere ; 287(Pt 3): 132287, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34563775

ABSTRACT

A scalable synthetic procedure for fabricating photoactive carbon dots (CD) from microcrystalline cellulose (MCC) is presented. The MCC was transformed into a photoactive nanosized CD by a one-step acid-assisted thermal-carbonization (~90 °C for 30 min). The efficiency of the obtained CD was determined by photo-removal of toxic hexavalent chromium (Cr(VI)) ions from wastewater. CD obtained from cellulose completely removed 20 ppm of Cr(VI) wastewater within ∼120 min under sunlight illumination. No Cr(VI) removal was observed in dark conditions and with control cellulose material as reference samples. The Cr(VI) removal follows pseudo-first-order kinetics along with a half-life of ∼26 min. Furthermore, the Cr(VI) removal from wastewater was supported via cyclic voltammetry analysis. Using a low-cost, naturally available cellulose material and sulfuric acid, the world's most-used chemical, creates techno-economic prerequisites for a scalable process of photoactive carbon dots.


Subject(s)
Water Pollutants, Chemical , Water Purification , Adsorption , Carbon , Cellulose , Chromium/analysis , Hydrogen-Ion Concentration , Kinetics , Sunlight , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
8.
ACS Appl Bio Mater ; 4(1): 252-266, 2021 01 18.
Article in English | MEDLINE | ID: mdl-35014282

ABSTRACT

Concentrically arranged multilayered fullerenes exhibiting onion-like morphology are popularly known as carbon nano-onion (CNO) and are useful in bioimaging application. On the basis of the origin of the fluorescence, the CNO-based nanoprobes are classified into type I and type II. The type I CNO-based nanoprobe needs a secondary moiety such as organic dyes or an amine functionalization at its surface to induce the fluorescence. On the other hand, the emission in type II does not originate from such an external surface passivating agent. The CNO-based system not only shows structural similarity to the well-known multiwalled carbon nanotube but is also a bit more advantageous because of its low cytotoxicity. These features enable their prolonged use in the biological system for imaging purposes. In particular, we have covered the aspects of synthesis, surface functionalization, the origin of fluorescence, and biocompatibility. In addition, recent developments directed toward in vitro and in vivo imaging studies by utilizing CNO-based nanoprobes are summarized here.


Subject(s)
Carbon/chemistry , Fluorescent Dyes/chemistry , Nanostructures/chemistry , Optical Imaging/methods , Animals , Biocompatible Materials/chemistry , Humans , Nanotubes, Carbon/chemistry , Neoplasms/diagnostic imaging , Quantum Dots/chemistry
9.
ACS Biomater Sci Eng ; 6(10): 5527-5537, 2020 10 12.
Article in English | MEDLINE | ID: mdl-33320561

ABSTRACT

Nanozymes have drawn significant scientific interest due to their high practical importance in terms of overcoming the instability, complicated synthesis, and high cost of protein enzymes. However, their activity is generally limited to particular pHs, especially acidic ones. Herein, we report that luminescent N, S, and P-co-doped carbon quantum dots (NSP-CQDs) act as attractive peroxidase mimetics in a wide pH range, even at neutral pH, for the peroxidase substrate 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in the presence of H2O2. The synergistic effects of multiple heteroatoms doping in CQDs boost the catalytic activity in a wide pH range attributed to the presence of high density of active sites for enzymatic-like catalysis and accelerated electron transfer during the peroxidase-like reactions. A possible reaction mechanism for the peroxidase-like activity of CQDs is investigated based on the radical trapping experiments. Moreover, the multifunctional activity of NSP-CQDs was further utilized for antibacterial assays for both Gram-negative and Gram-positive model species, including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. The growths of the employed E. coli and S. aureus were found to be significantly inhibited due to the peroxidase-mediated perturbation of cell walls. The present work signifies the current advance in the rational design of N, S, and P-co-doped CQDs as highly active peroxidase mimics for novel applications in diverse fields, including catalysis, medical diagnostics, environmental chemistry, and biotechnology.


Subject(s)
Quantum Dots , Anti-Bacterial Agents/pharmacology , Carbon , Escherichia coli , Hydrogen Peroxide , Peroxidases , Staphylococcus aureus
10.
Theranostics ; 10(17): 7841-7856, 2020.
Article in English | MEDLINE | ID: mdl-32685024

ABSTRACT

Rationale: The present study reports the multifunctional anticancer activity against B16F10 melanoma cancer cells and the bioimaging ability of fluorescent nitrogen-phosphorous-doped carbon dots (NPCDs). Methods: The NPCDs were synthesized using a single-step, thermal treatment and were characterized by TEM, XPS, fluorescence and UV-Vis spectroscopy, and FTIR analysis. The anticancer efficacy of NPCDs was confirmed by using cell viability assay, morphological evaluation, fluorescent live-dead cell assay, mitochondrial potential assay, ROS production, RT-PCR, western-blot analysis, siRNA transfection, and cellular bioimaging ability. Results: The NPCDs inhibited the proliferation of B16F10 melanoma cancer cells after 24 h of treatment and induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated levels of reactive oxygen species. The NPCDs treatment further elevated the levels of pro-apoptotic factors and down-regulated the level of Bcl2 (B-cell lymphoma 2) that weakened the mitochondrial membrane, and activated proteases such as caspases. Treatment with NPCDs also resulted in dose-dependent cell cycle arrest, as indicated by reduced cyclin-dependent kinase (CDK)-2, -4, and -6 protein levels and an enhanced level of p21. More importantly, the NPCDs induced the activation of autophagy by upregulating the protein expression levels of LC3-II and ATG-5 (autophagy-related-5) and by downregulating p62 level, validated by knockdown of ATG-5. Additionally, owing to their excellent luminescence property, these NPCDs were also applicable in cellular bioimaging, as evidenced by the microscopic fluorescence imaging of B16F10 melanoma cells. Conclusion: Based on these findings, we conclude that our newly synthesized NPCDs induced cell cycle arrest, autophagy, and apoptosis in B16F10 melanoma cells and presented good cellular bioimaging capability.


Subject(s)
Antineoplastic Agents/administration & dosage , Fluorescent Dyes/chemistry , Melanoma, Experimental/drug therapy , Quantum Dots/administration & dosage , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Autophagy/drug effects , Carbon/chemistry , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Humans , Intravital Microscopy/methods , Melanoma, Experimental/pathology , Mice , Microscopy, Fluorescence/methods , Nitrogen/chemistry , Phosphorus/chemistry , Quantum Dots/chemistry , Skin Neoplasms/pathology
11.
Drug Res (Stuttg) ; 70(11): 493-502, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32707592

ABSTRACT

An efficient and environmental benign solvent-free synthesis of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles (4A-E): was accomplished by grinding 3-chloro-6-hydrazinopyridazine (2): and ß-ketonitriles (3A-E): in the presence of p-toulenesulfonic acid as a catalyst. Subsequently, 6'-chloro group in 4A-E: was replaced with cyclic 2° amine derivatives viz. pyrrolidine 5A: , piperidine 5B: and morpholine 5C: to obtain 6A-E: , 7A-E: , 8A-E: respectively. The newly synthesized compounds were characterized by using IR, NMR (1H and 13C), mass spectral studies, elemental analyses. All the synthesized compounds were studied for their docking interaction with target protein 6COX and screened for their in vivo analgesic mode of action against swiss albino mice (animal model) using acetic-acid induced writhing test. Consequently, docking simulations data justifies the potential of synthesized series as an analgesic and very well correlated with in vivo study. Preliminary results revealed that most of the synthesized compounds exhibited moderate to good analgesic activity as compared to reference/standard drug (s) sodium diclofenac and candidates 4D: and 7C: protrude out as a promising lead for further investigation.


Subject(s)
Cyclooxygenase 2 Inhibitors/pharmacology , Drug Design , Pain/drug therapy , Pyrazoles/pharmacology , Pyridazines/pharmacology , Acetic Acid/administration & dosage , Acetic Acid/toxicity , Animals , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/ultrastructure , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Humans , Mice , Molecular Docking Simulation , Pain/chemically induced , Pyrazoles/chemistry , Pyrazoles/therapeutic use , Pyridazines/chemistry , Pyridazines/therapeutic use , Structure-Activity Relationship
12.
Biomicrofluidics ; 14(2): 024103, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32206158

ABSTRACT

Particle filtration and concentration have great significance in a multitude of applications. Physical filters are nearly indispensable in conventional separation processes. Similarly, microfabrication-based physical filters are gaining popularity as size-based particle sorters, separators, and prefiltration structures for microfluidics platforms. The work presented here introduces a linear combination of obstructions to provide size contrast-based particle separation. Polystyrene particles that are captured along the crossflow filters are packed in the direction of the dead-end filters. Separation of polydisperse suspension of 5 µm and 10 µm diameter polystyrene microspheres is attained with capture efficiency for larger particles as 95%. Blood suspension is used for biocharacterization of the device. A flow induced method is used to improve particle capture uniformity in a single microchannel and reduce microgap clogging to about 30%. This concept is extended to obtain semiquantification obtained by comparison of the initial particle concentration to captured-particle occupancy in a microfiltration channel.

13.
ACS Appl Bio Mater ; 3(6): 3656-3663, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-35025236

ABSTRACT

Nitrogen-sulfur codoped carbon dots (NSCD) were synthesized via a single-step microwave-assisted method having a fluorescence quantum yield of ∼12%. The NSCD has been proven to be nontoxic and utilized as a fluorescent imaging nanoprobe for cancer cells (HeLa cells) under UV and blue light excitation (in vitro environment). In addition to the long-known cell imaging application, these NSCD have been used as a sunlight active photomaterial for the removal of toxic hexavalent chromium as Cr(VI). The experimental results reveal that the sunlight active NSCD shows good potential toward the photocatalytic removal of Cr(VI) ions from the wastewater. For the environment and water purification purpose, three different wastewater samples were tested that are synthetic wastewater (up to 100 ppm), laboratory wastewater, and Cr(VI) ion-spiked industrial wastewater for the photocatalytic removal of Cr(VI). The biocompatible NSCD as a fluorescent imaging probe of cancer cells along with its fruitful utilization in photocatalysis under sunlight (compared to the dark condition) demonstrates the overall sustainability of the presented process.

14.
Eur J Med Chem ; 167: 226-244, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30772606

ABSTRACT

A series of new pyranocarbazole derivatives were synthesized via semi-synthetic modification of koenimbine (1a) and koenidine (1b) isolated from the leaves of Murraya koenigii. Among all, compound 3bg displayed significant anti-cancer activity against MDA-MB-231, DU145 and PC3 cell lines with the IC50 values of 3.8, 7.6 and 5.8 µM, respectively. It was also observed that the halogenated-benzyl substitution at N-9 position, C-3 Methyl and C-7 methoxy group on carbazole motif are favoured for anti-cancer activity. The detailed investigation was carried out with compound 3bg and its SEDDS (self-emulsifying drug delivery systems) formulation 3bgF. The in vivo drug release behavior study showed that the formulation enhanced slow release and better bioavailability at a tumor site. Compound 3bg and its formulation (3bgF) significantly inhibited cell proliferation and colony formation, induced G2/M arrest, reduced cellular ROS generation and induced caspase-dependent apoptosis in MDA-MB-231 cells. 3bg also induced significant alteration of Bax/Bcl expression ratio suggesting involvement of mitochondrial apoptosis. Additionally, 3bg caused down-regulation of mTOR/Akt survival pathway. 3bg do not bind to DNA, but interacts with tubulin as observed with in silico molecular docking studies. This interaction results in stabilization of tubulin polymerization similar to paclitaxel as detected in cell-free assay. Oral administration of 3bgF for 30 days at dose rate of 10 and 20 mg/kg body weight significantly reduced tumor growth in syngenic rat LA-7 mammary tumor model. These results indicated that the pyranocarbazole natural product based N-substituted analogues can act as potential anti-cancer lead.


Subject(s)
Antineoplastic Agents/chemical synthesis , Breast Neoplasms/drug therapy , Carbazoles/chemistry , Pyrans/chemistry , Tubulin/metabolism , Animals , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carbazoles/pharmacology , Caspases , Cell Line, Tumor , Down-Regulation/genetics , Humans , Inhibitory Concentration 50 , PC-3 Cells , Polymerization , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Pyrans/pharmacology , Rats , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism
15.
Nanoscale Adv ; 1(11): 4481-4491, 2019 Nov 05.
Article in English | MEDLINE | ID: mdl-36134401

ABSTRACT

Non-toxic amine-functionalized soluble graphene nano-sheets (f-GNS) were synthesized by using an old and well-known simple organic procedure. The f-GNS exhibited enhanced optical properties, such as strong blue fluorescence emission with a high value of quantum yield (∼13%). The O,O'-bis-(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol 800 as block polymeric amine (BPA)-passivized surface of f-GNS exhibited high aqueous solubility and excitation-dependent fluorescence emission behavior with a strong photo-stability performance. These f-GNS were tested for the significant selective sensing of toxic metal ions Cr(vi) and Hg(ii) from various tested toxic metal ions. The sensing experiment was supported by cyclic voltammetry analysis. The dual metal ion sensing method based on fluorescence showed the limit of detection (LOD) of ∼56 nM for Cr(vi) and ∼45 nM for Hg(ii) through a fluorescence quenching process. f-GNS were found to be non-toxic when tested over Escherichia coli (E.coli) cells. Additionally, the strong blue emission properties of f-GNS enabled their use as a suitable blue fluorescent ink under UV light illumination.

16.
Article in English | MEDLINE | ID: mdl-29697033

ABSTRACT

BACKGROUND: The benzimidazole ring is an important pharmacophore in modern drug discovery. Mannich reaction is one of the versatile reaction widely used in organic synthesis. Mannich base derivatives play an important role in medical field with diverse biological actions. OBJECTIVE: A series of N-(benzimidazol-1-ylmethyl)-4-chlorobenzamide derivatives (3a- 3m) were synthesized and evaluated for anti-inflammatory and antimicrobial potential. METHOD: Mannich reaction was used to synthesize N-(benzimidazol-1-ylmethyl)-4- chlorobenzamide analogues. The structures of novel target compounds were elucidated by spectral and analytical techniques and screened for in vivo anti-inflammatory activity and ulcerogenic activity. In addition, the prepared derivatives were also evaluated for in vitro antimicrobial activity against gram negative, gram positive and fungal strains. Further, in silico studies were carried out to define the interaction of the title compounds with COX-2 enzyme and microbial protein. RESULTS: The results revealed that out of thirteen molecules, compound 3a (containing chloromethyl substituent at 2-position of benzimidazole) showed significant antiinflammatory effect at a dose of 100 mg/kg p.o. and the experimental data was statistically significant at p≤0.05 level. Diclofenac sodium was taken as standard drug for antiinflammatory activity. Furthermore, derivative 3e (containing 2-chlorophenyl moiety at 2- position of benzimidazole scaffold) was found to be the most effective antimicrobial compound among the synthesized derivatives. Ciprofloxacin and clotrimazole were used as reference antimicrobial agents. Results from in vivo and in vitro studies of synthesized analogues were found to be in good correlation with in silico study. CONCLUSION: These results designate that N-(Benzimidazol-1-ylmethyl)-4-chlorobenzamide analogues, substituted with halogen functionality, could be used as potential lead for designing more potent anti-inflammatory and antimicrobial agents.


Subject(s)
Anti-Infective Agents , Anti-Inflammatory Agents , Benzimidazoles , Edema/drug therapy , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Aspergillus niger/drug effects , Aspergillus niger/growth & development , Bacteria/drug effects , Bacteria/growth & development , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use , Candida albicans/drug effects , Candida albicans/growth & development , Carrageenan , Edema/chemically induced , Female , Male , Molecular Docking Simulation , Rats, Wistar , Toxicity Tests, Acute
18.
Biomed Pharmacother ; 93: 510-521, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28675857

ABSTRACT

In recent years, many alkaloids of plant origin have attracted great attention due to their diverse range of biological properties including anti-hyperglycemic, anti-oxidant, anti-inflammatory, anti-diabetic and anti-tumor activity. Herein, the pyranocarbazole alkaloids were isolated from leaves of Murraya koenigii and their anti-cancer potential was investigated in different cancer cell lines. Among all tested compounds, murrayazoline and O-methylmurrayamine A demonstrated potent anti-cancer activity against DLD-1 colon cancer cells with the IC50 values of 5.7µM and 17.9µM, respectively, without any non-specific cytotoxicity against non-cancer HEK-293 and HaCaT cells. Further, studies of pure compounds revealed that the anti-cancer activity of compounds corresponds with altered cellular morphology, cell cycle arrest in G2/M phase, reactive oxygen species level and mitochondrial membrane depolarization of colon cancer cells. In addition, these compounds activated caspase-3 protein and upregulated Bax/Bcl-2 protein expression ratio leading to induction of caspase-dependent apoptosis in DLD-1 cells. These event induced by carbazole alkaloids also coincides with downregulation of Akt/mTOR suggesting downstream targeting of cell survival pathway. Thus, our in vitro studies not only provided scientific basis of the use of M. koenigii leaves in the traditional Indian Ayurveda medicines, but also expands possibilities of medicinal uses of M. koenigii leaves against colon cancer. Particularly, these findings will help in further investigating murrayazoline and O-methylmurrayamine A or their improvised derivatives as new therapeutics for the treatment of colon cancer.


Subject(s)
Apoptosis , Carbazoles/therapeutic use , Colonic Neoplasms/drug therapy , Down-Regulation , Mitochondria/metabolism , Murraya/chemistry , Plant Leaves/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Carbazoles/chemistry , Carbazoles/pharmacology , Caspases/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Shape/drug effects , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Down-Regulation/drug effects , Humans , Intracellular Space/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Phosphorylation/drug effects , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , TOR Serine-Threonine Kinases/metabolism
19.
Nanotechnology ; 28(18): 184002, 2017 May 05.
Article in English | MEDLINE | ID: mdl-28338473

ABSTRACT

We describe the super compressible and highly recoverable response of bucky sponges as they are struck by a heavy flat-punch striker. The bucky sponges studied here are structurally stable, self-assembled mixtures of multiwalled carbon nanotubes (MWCNTs) and carbon fibers (CFs). We engineered the microstructure of the sponges by controlling their porosity using different CF contents. Their mechanical properties and energy dissipation characteristics during impact loading are presented as a function of their composition. The inclusion of CFs improves the impact force damping by up to 50% and the specific damping capacity by up to 7% compared to bucky sponges without CFs. The sponges also exhibit significantly better stress mitigation characteristics compared to vertically aligned CNT foams of similar densities. We show that delamination occurs at the MWCNT-CF interfaces during unloading, and it arises from the heterogeneous fibrous microstructure of the bucky sponges.

20.
Toxicol Appl Pharmacol ; 309: 87-100, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27568862

ABSTRACT

Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10µM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1ß, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1ß/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide. Mechanistically, coagulin-L abrogated LPS induced total and mitochondrial ROS generation, NOX2, NOX4 mRNA expression, IRAK and MAPK (p38, JNK, ERK) activation. Coagulin-L also attenuated IκBα degradation, which prevented NFκB downstream iNOS expression and pro-inflammatory cytokine release. Furthermore, coagulin-L (10, 25, 50mg/kg, p.o.), undermined the LPS (10mg/kg, i.p.) induced endotoxemia response in mice as evinced from diminished cytokine release, nitric oxide, aortic p38 MAPK activation and endothelial tissue impairment besides suppressing NOX2 and NOX4 expression in liver and aorta. Moreover, coagulin-L also alleviated the ROS mediated oxidative damage which was assessed through protein carbonyl, lipid hydroperoxide, 8-isoprostane and 8-hydroxy-2-deoxyguanosine quantification. To extend, coagulin-L also suppressed carrageenan-induced paw edema and thioglycollate-induced peritonitis in mice. Therefore, coagulin-L can be of therapeutic importance in pathological conditions induced by oxidative damage.


Subject(s)
Mitochondria/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Toll-Like Receptor 4/metabolism , Withanolides/pharmacology , Animals , Cell Line , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Male , Mice , Mitochondria/immunology , NADPH Oxidases/metabolism
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