Human Genetics And Molecular Medicine - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/107

Browse

Author: search.filters.author.Arora, Sahil

Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Design, Synthesis, and Anticancer Evaluation of Hemithioindigos via Inhibition of Human Topoisomerases
    (John Wiley and Sons Inc, 2023-11-06T00:00:00) Kaur, Manpreet; Suman, Prabhat; Arora, Sahil; Singh, Tashvinder; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
    Hemithioindigos were designed as topoisomerase inhibitors, synthesized, and evaluated for their anticancer properties against lung (A549) and breast (MDA-MB-468 and MCF7) cancer cell lines. Among all the synthetics, three compounds exerted potential anticancer effects on A549 (lung) and MCF7 (breast) cancer cell lines at low micromolar concentrations. The results revealed that two of these compounds blocked the cancer cells at the G1/S phase, while the third compound showed moderate G2/M inhibition, leading to necrotic cell death. Finally, the topoisomerase inhibition assays revealed their potent Topo I/II inhibitory actions as one of the primary anticancer mechanisms. Molecular docking studies further corroborated these findings. � 2023 Wiley-VCH GmbH.
  • No Thumbnail Available
    Item
    ALK and ERBB2 Protein Inhibition is Involved in the Prevention of Lung Cancer Development by Vincamine
    (Bentham Science Publishers, 2023-04-13T00:00:00) Verma, Aarti; Yadav, Poonam; Rajput, Sonu; Verma, Saloni; Arora, Sahil; Kumar, Raj; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
    Background: According to the WHO report of 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. Objective: To find the potential targets of vincamine using a network pharmacology approach and docking studies and to evaluate the anti-cancer effect of vincamine on A549 cell line. Methods: Hence, in the present study, we explored the anti-cancer potential of vincamine by using network pharma-cology, molecular docking, and in vitro approaches. Network pharmacology demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. Results: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dose-dependent (0-500 ?M) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 ??. The wound-healing assay showed that vincamine treatment (150 and 300 ?M) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. Conclusion: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects. � 2023 Bentham Science Publishers.
  • No Thumbnail Available
    Item
    Design, Synthesis and Biological Evaluation of New 5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles as Topoisomerase Inhibitors
    (John Wiley and Sons Inc, 2021-07-09T00:00:00) Kaur, Manpreet; Mehta, Vikrant; Arora, Sahil; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
    5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles are designed as topoisomerase (Topo) inhibitors, synthesised and assessed for their anticancer properties against breast (MDA-MB-231 and MCF7), lung (A549), and colorectal (HCT116) cancer cell lines. All the compounds induced significant cytotoxicity at low micromolar concentration. The compound 5e exerted potential anticancer effects on breast cancer cell lines at a low micromolar level (IC50<2 ?M), and showed negligible toxicity towards normal cells. Compound 5 e reduced reactive oxygen species (ROS) level in breast cancer cells, altered mitochondrial membrane potential and induced the cell cycle arrest at the G2/M phase. This was accompanied by downregulation of oncogenic p-Akt and upregulation of p-PTEN along with modulation of apoptotic markers suggesting multiple mechanisms to reduce cancer cell viability. Finally, the topoisomerase inhibition assay revealed the inhibitory activity of 5 e against Topo I and Topo II. � 2021 Wiley-VCH GmbH.