Browsing by Author "Yadav, Umesh Prasad"

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Caulerpa taxifolia inhibits cell proliferation and induces oxidative stress in breast cancer cells
(Springer, 2018) Mehra, Richa; Bhushan, Satej; Yadav, Umesh Prasad; Bast, Felix; Singh, Sandeep
Caulerpa taxifolia (M. Vahl) C. Agardh or killer alga is known to possess several bioactive secondary metabolites with unique structural modifications. We investigated anti-oxidant and anti-proliferative activity of C. taxifolia extract (CTE) on breast and lung cancer cells, along with possible effects on mitochondrial membrane potential (MMP) and cell cycle progression. The results revealed up to 6-folds increase in reactive oxygen species (ROS), 2-folds increase in glutathione reductase (GR) activity, 1.7-fold increase in superoxide dismutase (SOD) activity and 1.8-fold change in catalase activity w.r.t. untreated cells i.e. 10.72 to 21.44 nmol/min/mL, 2.0 to 3.49 U/mL and 37.51 to 69.26 U/min/g FW, respectively, in MDA-MB-cells. Likewise, selective anti-proliferative activity with IC50 0.19 + 0.1, 0.27 + 0.1, and 0.43 + 0.1 μg/μL, was recorded in MDA-MB-231, T-47D, and H1299 cells. In addition, dose-dependent increase in MMP of up to 40% and G1/S phase mitotic arrest was documented by CTE treatment in MDA-MB-231 cells. The results suggest an anti-proliferative and oxidative stress inducing activity of CTE. Changes in MMP and cell cycle arrest further support the anti-cancer effects of CTE. It is believed that C. taxifolia may be considered as a potent source of anti-cancer drugs, subject to further validations.
Currently available COVID-19 management options
(Elsevier, 2023-01-20T00:00:00) Ludhiadch, Abhilash; Yadav, Umesh Prasad; Munshi, Anjana
The pandemic caused by new coronavirus (COVID-19), i.e., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started from the Wuhan state of China. COVID-19 is a novel infectious disease characterized by atypical pneumonia with the symptoms like fever, sore throat, fatigue, cough, and dyspnea. As of January 2022, more than 298 million people have been infected with SARS-CoV-2 (WHO). Changes in personal behavior like the use of face masks, proper hand hygiene, social distancing, and some interventions and control measures led by Governments all over the world resulted in decline of SARS-CoV-2 infections globally. The main concern of this pandemic is the risk of transmission and reinfection with new variants of COVID-19, and therefore, this COVID-19 pandemic is still a matter of great concern. It is a major challenge for clinicians and researchers worldwide to develop a specific strategy to eliminate this virus. The complications on account of COVID-19 disease manifest from mild to moderate. Only 5%�10% of the cases show severe and life-threatening complications with an approximately 2% of death rate worldwide [1]. Based on the severity of infection the National Institutes of Health (NIH) has classified COVID-19 into five different stages: asymptomatic infection, mild illness, moderate illness, severe illness, and critical illness [2]. Currently, many supportive measures such as ventilation systems and fluid management are being followed to save lives, but there is a dire need to develop antiviral treatment strategy to counter the spread of this virus completely. The treatment strategies also include blocking of enzymes or proteins that are essential for the survival of the virus, inhibition of viral structural proteins to prevent the affinity with human cells or virion formation, further by stimulating the immunity of the host, and inhibition of receptors in host that aid in entry of the virus. Currently, battling COVID-19 is the top most priority in the scientific world. Various pharmaceutical companies and research fraternities around the globe are working on interventions to reduce the impact of SARS-CoV-2 and prevent subsequent infections. Many clinical trials and animal studies are being carried out to identify the most potent drug alone or combination against the disease. The management of COVID-19 is being achieved by general treatment, specific treatments, and supplementation of vitamins and essential micronutrients like zinc and magnesium. General treatment strategies basically include antiviral therapies, antiinflammatory therapies and use of corticosteroids. The treatment of critically ill patients includes specific treatment strategies such as the use of anti-SARS-CoV-2 neutralizing antibody products, immunomodulatory agents, and oxygenation and ventilation management. Supplementation with vitamin C, vitamin D, magnesium, zinc, etc., is also being used to reduce the symptoms during the course of infection. SARS-CoV-2 infection also poses a risk of developing post-COVID-19 complications in the patients who suffered severe infection [3]. The management of post-COVID complications is currently under focus and there is a need to manage such patients with proper care. The post-COVID complications affect multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, hepatic, neuropsychiatric, hematologic, and several others. Developing a significantly potent treatment will help the medical fraternity to eradicate the virus without overburdening the existing healthcare system. This chapter has been compiled with an aim to sum up information on currently available treatment strategies and management for COVID-19. � 2023 Elsevier Inc. All rights reserved.
Design, synthesis and anticancer activity of 2-arylimidazo[1,2-a]pyridinyl-3-amines
(Academic Press Inc., 2021-11-01T00:00:00) Yadav, Umesh Prasad; Ansari, Arshad J.; Arora, Sahil; Joshi, Gaurav; Singh, Tashvinder; Kaur, Harsimrat; Dogra, Nilambra; Kumar, Raj; Kumar, Santosh; Sawant, Devesh M.; Singh, Sandeep
A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC50 values ranging from 1 to 5.5 ?M. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In-vitro enzyme assay showed selective topoisomerase II? inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using overexpression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression. � 2021 Elsevier Inc.
In Vivo Anticancer Evaluation of 6b, a Non-Covalent Imidazo[1,2-a]quinoxaline-Based Epidermal Growth Factor Receptor Inhibitor against Human Xenograft Tumor in Nude Mice
(MDPI, 2022-08-30T00:00:00) Bhat, Zahid Rafiq; Kumar, Manvendra; Sharma, Nisha; Yadav, Umesh Prasad; Singh, Tashvinder; Joshi, Gaurav; Pujala, Brahmam; Raja, Mohd; Chatterjee, Joydeep; Tikoo, Kulbhushan; Singh, Sandeep; Kumar, Raj
Tyrosine kinase inhibitors are validated therapeutic agents against EGFR-mutated non-small cell lung cancer (NSCLC). However, the associated critical side effects of these agents are inevitable, demanding more specific and efficient targeting agents. Recently, we have developed and reported a non-covalent imidazo[1,2-a]quinoxaline-based EGFR inhibitor (6b), which showed promising inhibitory activity against the gefitinib-resistant H1975(L858R/T790M) lung cancer cell line. In the present study, we further explored the 6b compound in vivo by employing the A549-induced xenograft model in nude mice. The results indicate that the administration of the 6b compound significantly abolished the growth of the tumor in the A549 xenograft nude mice. Whereas the control mice bearing tumors displayed a declining trend in the survival curve, treatment with the 6b compound improved the survival profile of mice. Moreover, the histological examination showed the cancer cell cytotoxicity of the 6b compound was characterized by cytoplasmic destruction observed in the stained section of the tumor tissues of treated mice. The immunoblotting and qPCR results further signified that 6b inhibited EGFR in tissue samples and consequently altered the downstream pathways mediated by EGFR, leading to a reduction in cancer growth. Therefore, the in vivo findings were in corroboration with the in vitro results, suggesting that 6b possessed potential anticancer activity against EGFR-dependent lung cancer. 6b also exhibited good stability in human and mouse liver microsomes. � 2022 by the authors.
Natural Compound-Based Nanoparticles to Target Free Radicals in Cancer
(Springer Singapore, 2022-09-28T00:00:00) Yadav, Umesh Prasad; Rhuthuparna, M.; Vasudeva, Kanika; Suman, Prabhat; Munshi, Anjana; Kumar, Santosh; Singh, Sandeep
Cell proliferation and malignant transformation are enabled by genetic and epigenetic changes. During the malignancy process, malignant cells acquire distinguishing characteristics. Cancer cells have acquired the ability to generate more reactive oxygen species (ROS), resulting in high oxidative stress. ROS-mediated signaling is needed for cancer cell physiology, and high levels of ROS cause oxidative stress-induced cytotoxicity in cancer cells. To avoid ROS-mediated cytotoxicity, cancer cells modulate their redox state through various antioxidant mechanisms and keep their ROS levels below the threshold. Cancer treatment that targets oxidative stress is an appealing option. Many natural oxidative stress modulators and bioactive compounds have been used in the treatment of cancer. Conventional uptake of bioactive molecule is associated with lower bioavailability, solubility, unlikely biodistribution, and side effects. Traditional drug uptake is improved by nanoformulation, making it easier to overcome side effects, improve biodistribution, and extend drug duration time. Natural prooxidant-loaded nanoparticles efficiently carry prooxidant to the tumor site and selectively and efficiently induce oxidative stress-mediated cell death in cancer cells. � Springer Nature Singapore Pte Ltd. 2022.