Browsing by Author "Sharma P."

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    E-pharmacophore guided discovery of pyrazolo[1,5-c]quinazolines as dual inhibitors of topoisomerase-I and histone deacetylase
    (Academic Press Inc., 2020) Joshi G.; Kalra S.; Yadav U.P.; Sharma P.; Singh P.K.; Amrutkar S.; Ansari A.J.; Kumar S.; Sharon A.; Sharma S.; Sawant D.M.; Banerjee U.C.; Singh S.; Kumar R.
    In the quest to ameliorate the camptothecin (CPT) downsides, we expedite to search for stable non-CPT analogues among 11 motifs of pyrazoloquinazolines reported. E-pharmacophore drug design approach helped filtering out pyrazolo[1,5-c]quinazolines as Topoisomerase I (TopoI) 'interfacial' inhibitors. Three compounds, 3c, 3e, and 3l were shown to be potent non-intercalating inhibitors of TopoI specifically and showed cancer cell-specific cytotoxicity in lung, breast and colon cancer cell lines. The compounds induced cell cycle arrest at S-phase, mitochondrial cell death pathway and modulated oxidative stress in cancer cells. Furthermore, a preliminary study was conducted to explore the feasibility of these compounds to be developed as dual TopoI-HDAC1 (histone deacetylase 1) inhibitors (4a) to combat resistance. Compound 4a was found to possess dual inhibitory capabilities in-vitro. Cytotoxic potential of 4a was found to be significantly higher than parent compound in 2D as well as 3D cancer cell models. Probable binding modes of 4a with TopoI and HDAC1 active sites were examined by molecular modelling.
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    Evaluation of leaves of Goniothalamus wynaadensis Bedd. for inhibition of metabolic viability of cancer cells & antimicrobial efficacy
    (Elsevier GmbH, 2019) Sharma A.; Sharma P.; Singh S.; Karegoudar T.B.; Holla H.
    Introduction: Goniothalamus wynaadensis Bedd. is a less explored medicinal plant belonging to the family Annonaceae. This species has been traditionally used by tribes of Wayanad, Kerala, in India, and also Indonesian tribes for joint-related ailments and also as a deodorizer. The aim of the study was to analyze leaf extracts of the plant for their antimicrobial and anticancer properties along with phytochemical screening. Methods: MTT assay was used to assess the cytotoxic potential of plant extracts against MDA-MB-231 and A-549. Antimicrobial potential of plant extracts was analyzed via liquid broth turbidometry assay and well in agar plate methods. Identification tests were carried out for phytochemical screening. Results: Antimicrobial assay showed EC50 values for ethyl acetate extract 0.82 mg/mL against Escherichia coli, 0.82 mg/mL against Salmonella typhi, & 0.88 mg/mL against Staphylococcus aureus which are quite significant. Other solvent extracts also displayed antimicrobial activities at varying dosage. MTT assay was performed at the dose concentrations of 1 ?g/mL, 5 ?g/mL & 25 ?g/mL, 50 ?g/mL and 100 ?g/mL to confirm the cytotoxicity of the extracts. The ethyl acetate extract displayed EC50 values of 4.96 ?g/mL against A-549 lung cancer cell line and 2.50 ?g/mL against MDA-MB-231 breast cancer cell line. Other extracts were also found to be cytotoxic. Conclusion: Ethyl acetate & water extracts have demonstrated potent activity against Salmonella typhi, Escherichia coli, & Staphylococcus aureus bacteria as well as, showing cytotoxicity against tested cancer cell lines. These results can be explored to identify individual phyto-molecules from the extracts with anticancer & antimicrobial potential.
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    Evaluation of the antioxidant, antibacterial and anticancer (lung cancer cell line A549) activity of: Punica granatum mediated silver nanoparticles
    (Royal Society of Chemistry, 2018) Annu; Ahmed S.; Kaur G.; Sharma P.; Singh S.; Ikram S.
    This work aimed to synthesize silver nanoparticles via an environmentally benign route, using the aqueous extract of Punica granatum as a precursor as well as a stabilizing and reducing agent. The as-synthesized silver nanoparticles were confirmed using UV-visible spectroscopy with an absorbance peak at 450 nm and were thereafter further confirmed using dynamic light scattering (DLS), High Resolution Transmission Electron Microscopy (HR-TEM) and X-Ray Diffraction (XRD). TEM analysis revealed 6-45 nm and spherically dispersed nanoparticles and XRD showed the crystalline nature of the nanoparticles. The free radical scavenging activity of the nanoparticles for DPPH and intracellular reactive oxidative species (ROS) production were observed using dihydroethidium (DHE) non-fluorescent stain and a CellROX® Deep Red fluorescent probe. Antibacterial assays against the most common Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus) bacteria showed a higher zone of inhibition against S. aureus. Furthermore, the anti-cancerous activity of the biologically synthesized silver nanoparticles was revealed by the inhibited cell growth of lung cancer A549 cells and no cytotoxicity was observed. This may be due to their ability to arrest the cell cycle at G1 phase. Thus, this work provides a gateway to explore more about the anticancer properties of biogenically synthesized silver nanoparticles and these biologically prepared silver nanoparticles have the potential to be utilized in biomedical science.
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    P53-mediated anticancer activity of Citrullus colocynthis extracts
    (Bentham Science Publishers, 2019) Joshi G.; Kaur J.; Sharma P.; Kaur G.; Bhandari Y.; Kumar R.; Singh S.
    Background: Current anticancer therapeutics comes with significant side effects and thus focus is shifting towards minimizing the side effects or to avoid the disease altogether. Thus, various natural products are being investigated for their potential therapeutic values which can be easily included in daily diet of a person. Citrullus colocynthis (L.) fruit is commonly used in traditional medicines and is known to have antioxidant effects, thus may possess potent anticancer activity as well. Objectives: To establish the anticancer potential of fruit belonging to Citrullus colocynthis (L.) and delineate the potential targets. Results: In the present study it was found that seed and pulp extracts of the fruit are effective against various cancer cell lines while the normal cells, with lower rate of division, remain largely unaffected. The current study for the first time shows that these extracts function via regulation of p53 pathways and the mode of apoptosis is mostly via mitochondrial (intrinsic) pathway. The biological profiling of the extracts was also validated using molecular modelling studies utilizing the two major polyphenols constituents from colocynths i.e., Isoorientin and Isovitexin. Conclusion: The study suggested that the constituent has a multiple target approach for the inhibition of cancer cell proliferation and inhibition of ROS production via the major apoptotic proteins. All of these outcomes suggest and establish a critical role of ROS accumulation and mitochondrial function in the p53-dependent cell.
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    Patterns of plant communities along vertical gradient in Dhauladhar Mountains in Lesser Himalayas in North-Western India
    (Elsevier B.V., 2020) Ahmad M.; Uniyal S.K.; Batish D.R.; Singh H.P.; Jaryan V.; Rathee S.; Sharma P.; Kohli R.K.
    Mountains are definitely the most rugged, yet frail resources and biodiversity-rich regions of the world. Environmental variables directly affect species composition, growth patterns, and the ecosystem resulting in a drastic change in the vegetation composition along ascending elevations. The present study investigated vegetation composition, nestedness, and turnover in plant communities along a vertical gradient (2000 to 4000 m) in Dhauladhar Mountains, Lesser Himalayas, India. We determined how ?-diversity pattern and nestedness-related processes or turnover (?-diversity) causes dissimilarity in plant communities' composition along the vertical gradient. Overall, 21 permanent plots (20 � 20 m2) at every 100 m interval from 2000 to 4000 m were established. A sampling of shrubs and herbaceous species was done by marking sub-plots of 5 � 5 m2 and 1 � 1 m2, respectively, within permanent plots. We observed an inverted hump-shaped pattern for evenness index (E), a unimodal hump-shaped pattern for Shannon index (H?), Margalef's richness index, and ?-Whittaker (?w) diversity, and mild-hump-shaped pattern for Simpson index (?) across the elevational gradient. Turnover (?sim) and the nestedness-resultant component of ?-diversity (?sne) significantly differed across the elevational gradient. The observed ?-diversity patterns revealed that the species replacement rate was less in the mid-altitude communities as compared to lower and higher altitude communities. It was largely attributed to the ecotonic nature of mid-altitudes, which benefited mid-elevational communities rather than low or high altitude communities. Besides lower altitudes, the increased human interference has led to disturbance and subsequent homogenization of flora across the mid-altitudes. With respect to this, the present study signifies the need for preserving the mid-altitudinal communities, without undermining the importance of conserving the low and high altitude communities. � 2020 Elsevier B.V.
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    Small regulatory molecules acting big in cancer: Potential role of mito-miRs in cancer
    (Bentham Science Publishers, 2019) Sharma P.; Bharat; Dogra N.; Singh S.
    MicroRNAs [miRNAs] are short, non-coding, single stranded RNA molecules regulating gene expression of their targets at the posttranscriptional level by either degrading mRNA or by inhibiting translation. Previously, miRNAs have been reported to be present inside the mitochondria and these miRNAs have been termed as mito-miRs. Origin of these mito-miRs may either be from mitochondrial genome or import from nucleus. The second class of mito-miRs makes it important to unravel the involvement of miRNAs in crosstalk between nucleus and mitochondria. Since miRNAs are involved in various physiological processes, their deregulation is often associated with disease progression, including cancer. The current review focuses on the involvement of miRNAs in different mitochondrial mediated processes. It also highlights the importance of exploring the interaction of miRNAs with mitochondrial genome, which may lead to the development of small regulatory RNA based therapeutic options.