Pharmaceutical Sciences and Natural Products - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56

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Author: search.filters.author.Sharma, Praveen

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    Exploring the COVID-19 vaccine candidates against SARS-CoV-2 and its variants: where do we stand and where do we go?
    (Taylor and Francis Ltd., 2021-12-03T00:00:00) Joshi, Gaurav; Borah, Pobitra; Thakur, Shweta; Sharma, Praveen; Mayank; Poduri, Ramarao
    As of September 2021, 117 COVID-19 vaccines are in clinical development, and 194 are in preclinical development as per the World Health Organization (WHO) published draft landscape. Among the 117 vaccines undergoing clinical trials, the major platforms include protein subunit; RNA; inactivated virus; viral vector, among others. So far, USFDA recognized to approve the Pfizer-BioNTech (Comirnaty) COVID-19 vaccine for its full use in individuals of 16�years of age and older. Though the approved vaccines are being manufactured at a tremendous pace, the wealthiest countries have about 28% of total vaccines despite possessing only 10.8% of the total world population, suggesting an inequity of vaccine distribution. The review comprehensively summarizes the history of vaccines, mainly focusing on vaccines for SARS-CoV-2. The review also connects relevant topics, including measurement of vaccines efficacy against SARS-CoV-2 and its variants, associated challenges, and limitations, as hurdles in global vaccination are also kept forth. � 2021 Taylor & Francis Group, LLC.
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    Synthesis, in vitro, and docking analysis of c-3 substituted coumarin analogues as anticancer agents
    (Bentham Science Publishers, 2020-01-28T00:00:00) Thakur, Anuradha; Kaur, Kamalpreet; Sharma, Praveen; Singla, Ramit; Singh, Sandeep; Jaitak, Vikas
    Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effects along with multidrug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-? target protein by molecular docking. Methods: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues, 12 and 13 show good antiproliferative activity with IC50 values 1 and 1.3 ?M, respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit a docking score of -4.10 kcal/mol and -4.38 kcal/mol, respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future. � 2021 Bentham Science Publishers.
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    Synthesis and biological evaluation of pyrimidine bridged combretastatin derivatives as potential anticancer agents and mechanistic studies
    (Academic Press Inc., 2018) Kumar, Bhupinder; Sharma, Praveen; Gupta, Vivek Prakash; Khullar, Madhu; Singh, Sandeep; Dogra, Nilambra; Kumar, Vinod
    A number of pyrimidine bridged combretastatin derivatives were designed, synthesized and evaluated for anticancer activities against breast cancer (MCF-7) and lung cancer (A549) cell lines using MTT assays. Most of the synthesized compounds displayed good anticancer activity with IC50 values in low micro-molar range. Compounds 4a and 4p were found most potent in the series with IC50 values of 4.67 ?M & 3.38 ?M and 4.63 ?M & 3.71 ?M against MCF7 and A549 cancer cell lines, respectively. Biological evaluation of these compounds showed that selective cancer cell toxicity (in vitro using human lung and breast cancer cell lines) might be due to the inhibition of antioxidant enzymes instigating elevated ROS levels which triggers intrinsic apoptotic pathways. These compounds were found nontoxic to the normal human primary cells. Compound 4a, was found to be competitive inhibitor of colchicine and in the tubulin binding assay it showed tubulin polymerization inhibition potential comparable to colchicine. The molecular modeling studies also showed that the synthesized compounds fit well in the colchicine-binding pocket. ? 2018 Elsevier Inc.
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    Dual inhibitors of epidermal growth factor receptor and topoisomerase IIa derived from a quinoline scaffold
    (Royal Society of Chemistry, 2016) Chauhan, Monika; Joshi, Gaurav; Kler, Harveen; Kashyap, Archana; Amrutkar, Suyog M.; Sharma, Praveen; Bhilare, Kiran D.; Banerjee, Uttam C.; Singh, Sandeep; Kumar, Raj
    Based on the quinazoline bearing EGFR inhibitors, a series of thirty four compounds having a quinoline scaffold were synthesised and evaluated in vitro for EGFR kinase inhibitory activity. A structure-activity relationship study revealed that 2,4-bis(arylamino) substituted quinolines possessed better anti-EGFR kinase activity. Compounds 3f and 3m emerged as potent EGFR kinase inhibitors (200 and 210 nM, respectively) and showed excellent anticancer activity at the micromolar level against a panel of cancer cell lines comparable to erlotinib. Furthermore, representative compounds inhibited the human topoisomerase II? selectively and catalytically, did not intercalate with DNA, increased intracellular ROS concentration (except 3m) and altered the mitochondrial membrane potential of the cancer cells. Cell cycle analysis and annexin-V staining in a lung cancer cell line showed that the compounds delayed cell cycle progression by inducing cell cycle arrest and subsequent apoptosis at the G1 phase. The facts were further corroborated through molecular modeling studies. ? 2018 The Royal Society of Chemistry.
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    Pyrimidine containing epidermal growth factor receptor kinase inhibitors: Synthesis and biological evaluation
    (Blackwell Publishing Ltd, 2017) Joshi, Gaurav; Nayyar, Himanshu; Kalra, Sourav; Sharma, Praveen; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
    Structure-based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a?d are reported. The compounds (1a?d) inhibited the EGFR kinase activity in vitro with IC50 range 740?nm to 3??m. mRNA expression of EGFR downstream target genes, that is twist, c-fos and aurora were found to be altered upon treatment with compounds 1a?d. The compounds 1a?d exhibited excellent anticancer activity at low micromolar level (3.2?9??m) in lung, colon and breast cancer cell lines. Furthermore, compounds induced the alteration in mitochondrial membrane potential and reactive oxygen species level and. Selected compound 1b was found to increase sub-G1 population indicative of cell death, the mode of cell death was apoptotic as evident from Annexin V verses propidium iodide assay. Molecular modelling further helped to investigate the binding recognition pattern of the compounds in ATP binding EGFR domain similar to erlotinib and dissimilar to WZ4002. ? 2017 John Wiley & Sons A/S.