Tyrosine kinase receptors promote the growth and differentiation of normal breast and malignant human breast cancer cells, known as ERBB receptors. Various ERBB receptors are EGFR/ErbB1 and ErbB2/neu, which get over expressed in different solid tumors that activate upon binding of ligand to the extra cellular domain of these receptors. Of note, the epidermal growth factor receptor (EGFR) is a prime contributor to cancer through the involvement of four receptor tyrosine kinases (RTKs), namely, HER1, HER2, HER3, and HER4. Among them, HER2 and HER4 are majorly associated with breast cancer. Non-peptide quinazoline compounds homologous of the adenosine triphosphate (ATP) are competitively inhibited to RTKs to prevent cancer growth and metastasis. Various small drug molecule that targets the RTKs having the same scaffold, includes Lapatinib, Tivozanib, Erlotinib, Gefitinib, Crizotinib, and Ceritinib. The present study aims to investigate the comparative potential of structurally similar TKIs against HER2 and HER4 receptor receptors-silico molecular docking using FlexX software (LeadIT 2.3.2). Each docked complex's interaction profile was performed using BIOVIA Discovery Studio Visualizer 4.0. Molecular docking analysis was performed in order to get deeper insights into the interaction and binding pattern of the ligands with HER2 and HER4 receptors. The docking results revealed the Lapatinib compound acquired the relatively highest binding score of -32.36 kcal/mol and -35.76 kcal/mol with HER2 and HER4 proteins, respectively, concerning other compounds. Lapatinib is identified as a potential inhibitor for both the RTKs. Our study thus suggests the probable direction that could be further explored in inhibiting EGFR protein harbouring breast cancer.
Abstract-Wireless Sensor Network (WSN) is the collection of several sensor nodes which are able to send their sensed data to base station. In dense WSN, consecutive observations obtained by sensors are spatial as well as temporally correlated in applications that involve the observation of the variation of a physical phenomenon. These sensor nodes are battery driven, therefore an efficient utilization of power is essential in order to reduce data traffic inside sensor networks and thus reduce amount of data that need to send to base station for enhancing the network lifetime. For this reason data aggregation is used. The correlation degree gives a correlation measurement that measures the correlation between a sensor node's data and its neighboring sensor nodes' data. The resulting representative data obtained using the proposed methods have a lower data distortion than those obtained earlier. Also, to construct an energy balanced network in data transmitting process, the energy of every sensor nodes should be considered and Fuzzy Logic is also used to determine an optimal routing path from the source to the destination by maintaining the highest remaining battery power, minimum traffic loads and minimum number of hops.
Objectives: Substituted quinazolin-4(3H)-ones at position-3 with phenyl ring, heterocycles and aliphatic moieties, were reported to impart antimicrobial activities. In light of this, we have attempted to prepare a novel series of 2-pheny-3-substituted quinazolin-4(3H)-ones fused with an azomethine (-CH=N-) connection to Benzylidene and ethylidene motifs. Each of these motifs underwent testing to determine whether it could inhibit in-vitro microbial DHFR and the subsequent antimicrobial action. Materials and Methods: The synthesized 2-phenyl-3substituted quinazolin-4(3H)-ones were characterized by FT-IR, 1 H-NMR, 13 C-NMR, ESI-MS and elemental (C, H, N, O and X=halogen) analysis. Evaluated results of in-vitro microbial DHFR inhibition are compared with the reported drug trimethoprim. Agar disc diffusion method was used for in-vitro antimicrobial activity, performed against pathogenic Gram-positive and Gramnegative bacteria like Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, Pseudomonas aeruginosa respectively, and fungi like Candida albicans, and Aspergillus niger. Results: Docking analysis of ligands with DHFR (PDB=2W3M) has shown strong hydrophobic binding interaction and confirmed a perfect fit into the active domain of the target protein. Possible antimicrobial activity was induced from microbial DHFR inhibition. The results of the tests are compared with gentamycin, ciprofloxacin, and clotrimazole. Compounds with potent antibacterial activity were QI-j, and QII-f (MIC=0.1-0.2µg/mL), and moderately active compounds were QIa-d, QIl-m, QIII-d, and QIIIe-f (MIC=0.5-2.0µg/mL). Compounds exhibited potent antifungal activity were QI-c, QII-b, and QIII-f (MIC=0.1-0.2µg/mL), moderately active compounds were QIc-e, QI-g, QIm-n, QII-d, QIII-b, and QIII-e (MIC=0.5-2.0µg/mL). Conclusion: Particularly test compounds have produced DHFR inhibition in a range of 4-24µM as compared with trimethoprim (IC 50 =10 µM). Benzylidene and ethylidene moieties attached to the quinazolin-4(3H)-one had contributed to this activity. Present series of substituted quinazolin-4(3H)-ones provide a path for the design and development of newer antimicrobial agents in the treatment of deadly pathogenic infections.
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