Browsing by Author "Charbe, Nitin"

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    An overview of vaccine development for COVID-19
    (2021) Shahcheraghi, Seyed H.; Ayatollahi, Jamshid; Aljabali, Alaa A. A.; Shastri, Madhur D.; Shukla, Shakti D.; Chellappan, Dinesh K.; Jha, Niraj K.; Anand, Krishnan; Katari, Naresh K.; Mehta, Meenu; Satija, Saurabh; Dureja, Harish; Mishra, Vijay; Almutary, Abdulmajeed G.; Alnuqaydan, Abdullah M.; Charbe, Nitin; Prasher, Parteek; Gupta, Gaurav; Dua, Kamal; Lotfi, Marzieh; Bakshi, Hamid A.; Tambuwala, Murtaza M.
    The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.
  • No Thumbnail Available
    Item
    Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens
    (2020) Pardhi, Dinesh M.; Karaman, Didem Sen; Timonen, Juri; Wu, Wei; Zhang, Qi; Satija, Saurabh; Mehta, Meenu; Charbe, Nitin; McCarron, Paul A.; Tambuwala, Murtaza M.; Bakshi, Hamid A.; Negi, Poonam; Aljabali, Alaa A.; Dua, Kamal; Chellappan, Dinesh K.; Behera, Ajit; Pathak, Kamla; Watharkar, Ritesh B.; Rautio, Jarkko; Rosenholm, Jessica M.
    This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.
  • No Thumbnail Available
    Item
    Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation
    (2020) Santana-Romo, Fabian; Lagos, Carlos F.; Duarte, Yorley; Castillo, Francisco; Moglie, Yanina; Maestro, Miguel A.; Charbe, Nitin; Zacconi, Flavia C.
    The coagulation cascade is the process of the conversion of soluble fibrinogen to insoluble fibrin that terminates in production of a clot. Factor Xa (FXa) is a serine protease involved in the blood coagulation cascade. Moreover, FXa plays a vital role in the enzymatic sequence which ends with the thrombus production. Thrombosis is a common causal pathology for three widespread cardiovascular syndromes: acute coronary syndrome (ACS), venous thromboembolism (VTE), and strokes. In this research a series of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives as a potential factor Xa (FXa) inhibitor were designed, synthesized, and evaluated for their FXa inhibitor activity, cytotoxicity activity and coagulation parameters. Rational design for the desired novel molecules was performed through protein-ligand complexes selection and ligand clustering. The microwave-assisted synthetic strategy of selected compounds was carried out by using Ullmann-Goldberg, N-propargylation, Mannich addition, Friedel-Crafts, and 1,3-dipolar cycloaddition type reactions under microwave irradiation. The microwave methodology proved to be an efficient way to obtain all novel compounds in high yields (73-93%). Furthermore, a thermochemical analysis, optimization and reactivity indexes such as electronic chemical potential (mu), chemical hardness (eta), and electrophilicity (omega) were performed to understand the relationship between the structure and the energetic behavior of all the series. Then, in vitro analysis showed that compounds 27, 29-31, and 34 exhibited inhibitory activity against FXa and the corresponding half maximal inhibitory concentration (IC50) values were calculated. Next, a cell viability assay in HEK293 and HepG2 cell lines, and coagulation parameters (anti FXa, Prothrombin time (PT), activated Partial Thromboplastin Time (aPTT)) of the most active novel molecules were performed to determine the corresponding cytotoxicity and possible action on clotting pathways. The obtained results suggest that compounds 27 and 29 inhibited FXa targeting through coagulation factors in the intrinsic and extrinsic pathways. However, compound 34 may target coagulation FXa mainly by the extrinsic and common pathway. Interestingly, the most active compounds in relation to the inhibition activity against FXa and coagulation parameters did not show toxicity at the performed coagulation assay concentrations. Finally, docking studies confirmed the preferential binding mode of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives inside the active site of FXa.
  • No Thumbnail Available
    Item
    Targeting LIN28: a new hope in prostate cancer theranostics
    (2021) Shrivastava, Garima; Aljabali, Alaa A. A.; Shahcheraghi, Seyed Hossein; Lotfi, Marzieh; Shastri, Madhur D.; Shukla, Shakti D.; Chellappan, Dinesh K.; Jha, Niraj Kumar; Anand, Krishnan; Dureja, Harish; Pabari, Ritesh M.; Mishra, Vijay; Almutary, Abdulmajeed G.; Alnuqaydan, Abdullah M.; Charbe, Nitin; Prasher, Parteek; Negi, Poonam; Goyal, Rohit; Dua, Kamal; Gupta, Gaurav; Serrano-Aroca, Angel; Bahar, Bojlul; Barh, Debmalya; Panda, Pritam Kumar; Takayama, Kazuo; Lundstorm, Kenneth; McCarron, Paul; Bakshi, Hamid; Tambuwala, Murtaza M.
    The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.