KDR/VEGFR-2 Receptor Tyrosine Kinase Inhibitors and 3D QSAR
(CoMFA and CoMSIA) Study
Arun Kumar Yasala1*, Tausif Khan2
1Department of Biotechnology, University of Hyderabad, Hyderabad, India
2Department of Microbiology, SGRR, Dehradun, India
- *Corresponding Author:
- Arun Kumar Yasala
Department of Biotechnology
University of Hyderabad, Hyderabad, India
Received Date: 12/08/2016; Accepted Date: 12/08/2016; Published Date: 28/08/2016
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The review illustrates on the Vascular endothelial growth factor-A (VEGF-A) which shows pivotal roles in many angiogenic processes both in stable and pathological condition. Angiogenesis plays a key role in a number of pathology conditions with VEGFR-2 signals implicated in both tumour angiogenesis and diabetic retinopathy.
3D-QSAR, CoMFA, CoMSIA, VEGFR-2, VEGF-A.
The intricated, branched circulatory networks of vascular endothelial and supporting cells is essential for transporting oxygen, essential nutrients, and signaling molecules, removing of carbon dioxide and metabolic end products from cells, tissues, and organs. The process of development and growth of new capillary blood vessels from pre-existing vessels is called as Angiogenesis. It occurs in different physiological processes such as reproductive functions (ovular cycle, formation of the placenta), tissue repair (closing up of wounds and ulcers), inflammation [1-5] and ischemia [6-8]. Angiogenesis can however become pathological and contribute to the development of certain diseases like diabetic proliferative retinopathy , rheumatoidic polyarthritis [10,11], atherosclerosis, development of numerous types of tumors and the formation of metastases .
Vascular endothelial growth factor-A (VEGF-A) plays pivotal roles in many angiogenic processes both in normal and pathological conditions. VEGF-A [13,14] binds its tyrosine kinase receptor VEGFR-2 (Flk-1/KDR, Fetal liver kinase-1/Kinase insert Domain containing Receptor) with high affnity and regulates angiogenesis during the development of solid tumors [15-20]. Flk-1 is the murine homologue of human KDR, sharing 85% sequence homology and being 2 amino acids shorter.
Vegf Ligands And Receptors
Vascular endothelial growing factor (VEGF) represents a family of homodimeric glycoproteins which are most important for the embryonic development of the blood vascular system (vasculogenesis) , lymphatic system (lymphangiogenesis) [22-24] and in the new blood formation from pre-existing vessels (angiogenesis). In mammals, the VEGF family contains five members, VEGF-A, VEGF-B, VEGF-C, VEGF-D and placenta growth factor (PLGF).Members of the VEGF family reflects different affinities for one of the three VEGF tyrosine kinase receptors: VEGF receptor VEGFR-1, VEGFR-2 and VEGFR-3 .
VEGF-A binds to both VEGFR-1 and VEGFR-2, PLGF and VEGF-B bind exclusively to VEGFR-1.VEGF-C and VEGF-D pro-peptides are expressed initially as that bind the VEGFR-3. The mature, proteolytically processed VEGF-C and VEGF-D ligands can also bind to VEGFR-2.
VEGFR-1 (Flt-1) expresses on haematopoietic stem cells [25-27], monocytes, macrophages [28-30] and vascular endothelial cells which is critical for haematopoietic cell development.VEGFR-2 (Flk-1/KDR) is shown on vascular endothelial cells and lymphatic endothelial cells and is critical for vascular endothelial cell development.VEGFR-3 (Flt4) expression is restricted to lymphatic endothelial cells and is critical for lymphatic endothelial cell development.
Vegf-A And Its Receptor Vegfr-2
The human VEGF-A gene is located on chromosome 6p21.3. The coding area spans exactly 14 kb and contains eight exons. In mammals, VEGF-A exists in a number of different isoforms following alternative cutting of a single precursor mRNA. In humans, six VEGF-A splice variants have been detected: VEGF-A189, VEGF-A121, VEGF-A165, VEGF-A145, VEGF-A183 and VEGF-A206. VEGF-A165 is the most abundant and biologically active form and is expressed as a 46 kDa homodimer  formed of two 23 kDa subunits. VEGF-A is produced by a range of cells including smooth muscle vascular cells, macrophages and tumour cells.
VEGFR-2 is a type III transmembrane kinase receptor. The human VEGFR-2 gene, located on chromosomes 4q11–q12 encodes a full-length receptor of 1356 amino acids. It contains of an extracellular region formed of seven immunoglobulin [32-34] (Ig)-like domains, a short transmembrane domain, and a intracellular region consisting of single tyrosine kinase [35,36] domain, split by a 70 amino-acid insert. VEGFR-2 protein is initially translated as a 150 kDa protein inside the cell without significant glycosylation [37-39]. It is then processed by a chain of glycosylations to form a mature 230 kDa form that is expressed on the cell surface.
VEGF-A binds to the second and third extracellular Ig-like domains of VEGFR-2. Ligand binding induces receptor dimerisation and autophosphorylation. The binding of the dimeric VEGF ligand, to the Ig-like domains 2 and 3 of one receptor monomer [40,41], increases the probability of the second receptor monomer ties the already tethered ligand.
Once the two receptors are cross-linked to each other with simultaneous interaction via the ligand, their membrane-proximal Ig-like domains are held in close proximity so that low-affinity homotypic interactions among these domains further stabilises the receptor dimers. This allows for the exact positioning of the intracellular kinase domains resulting in autophosphorylation.
The major phosphorylation [42-44] sites are Y951 present in kinase-insert domain, Y1054 and Y1059 within the kinase domain, and Y1175 and Y1214 in the C-terminal tail of the receptor. Phosphorylation of specific tyrosine residues in the receptor creates a consensus sequence for the deployment of specific intracellular signalling proteins, via their Src homology 2 (SH2) domains. Phosphorylation [45-47] of Y951 creates a binding forming site for VEGF-receptor-association in protein (VRAP) also called T-cell-specific adapter molecule (TSAd). Phosphorylation of Y1175 creates a binding site for a number of signalling proteins such as PLC-γ , the adaptor protein Shb and the adaptor protein Sck. Phosphorylation of Y1214 creates a binding site for the adaptor protein Nck.
vegfr-2 signalling in tumour angiogenesis and therapeutic inhibition
Angiogenesis plays a role in a number of pathological conditions with VEGFR-2 signalling applied in both tumour angiogenesis and diabetic retinopathy [48-50]. Angiogenesis is very important for tumour formation as cancer cells have a relatively high metabolic demand for oxygen and nutrients to continous growth. How ever, the capillary and vascular network allows tumours to metastasise and spread to other sites in the body.
VEGF-A expression in cancer cells is induced during tumour formation by environmental stimuli such as hypoxia (low Oxygen tension) or by mutational genes of tumour suppressor genes (K-ras, p53 or HER2/ErbB2) or by activation of oncogenes [51,52]. Expression of VEGFR-2 is upregulated in the tumour vasculature compared with normal vasculature. Indeed, VEGFR-2 expression is a prognostic marker in the clinical outcome of patients with a variety of malignancies.
In 1971, Folkman first proposed the theory that stops angiogenesis which results in the arrest of tumour growth. This vision has now become a reality, with the arrival of a number of anti-angiogenic drugs in the clinic. These agents can be divided in two broader classes, some agents targeting the VEGF ligand and agents targeting the cell surface receptor.
Bevacizumab (Avastin®) [53-57] was afflicated the first anti-angiogenic drug to receive FDA approval for cancer treatment [58-60] and in february 2004, it was passed for use in combination with 5-fluorouracil-based chemotherapy for treatment of metastatic colorectal cancer [61-63]. Avastin is a humanised recombinant monoclonal IgG1 antibody which binds to and inhibits the biological activity of all VEGF-A isoforms.Now this drug is in clinical trails for use against a range of different cancers in combination with chemotherapy.
A number of pharmaceutical organisations and companies have developed small molecule inhibitors of the VEGFRs. These agents target RTKs and their ATP-binding sites, resulting in the blockade of downstream intracellular signalling pathways. Sunitinib [63-66] (Sutent®) is a two way targeting RTK inhibitor to VEGFR-2 and PDGFR-β, which exhibits anti-tumour activity.
Therefore, inhibition of the VEGFR-2 has evolved in an attractive strategy in the treatment of cancers.
Quantitative Structure Activity Relationship (Qsar)
The number of compounds necessary for synthesis in order to study their bioactivities against a receptor experimentally using bioassays by placing 10 different substitution groups in 4 positions of benzene ring is 104.This takes huge amount of time as each compound has to be synthesized and tested for bioactivity [67-70] against receptor individually. The solution is to synthesize a small number of compounds and from their data deriving rules to predict the biological activity [71,72] of other analogous compounds. This enables the study of several substitutions on a common core in less time.
A QSAR is a mathematical bonding between biological activity of a molecular system and its geometric/chemical characteristics. QSAR attempts to find bonding between biological activity and molecular properties, so that these “rules” can be used to evaluate the activity of new compounds. These molecular properties/descriptors include parameters to account for hydrophobicity [73-76], topology [77-79], electronic properties [80,81], steric effects etc., which are determined empirically or by computational methods and activities used in QSAR model generation include measurements (IC50, EC50, ED50, Ki, etc.) from biological assays.
QSAR's most general mathematical form is: Activity=f (physiochemical and/or structural properties).
Structure-activity relationships of traditional type for e.g., Hansch analysis usually do not take the 3D structures of the investigated compounds into account in an explicit manner. Instead, they use substituent parameters and indicator variables to describe the structural variations [82,83]. Extensions to the traditional QSAR approaches have been developed which explicitly uses geometry of the structures during the development of a QSAR model [84-87]. These new technologies are commonly referred as 3D-QSAR methodologies.
The presently most used 3D-QSAR techniques are:
CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis).
CoMFA is based on the assumption that changes in biological activity correlate with changes in the steric and electrostatic fields of molecules. It calculates steric fields using Lennard-Jones potential and electrostatic fields using a Coulombic potential.
The following steps have to be considered to develop a CoMFA model:
1. Selection of training set compounds
2. Identification of active conformations
3. Molecular alignment
4. Calculation of field values
5. Partial Least Square (PLS) analysis
6. Validation using test set compounds
7. Interpretation of results (contour maps)
8. Predictions of new compounds
CoMSIA is an extension of the CoMFA methodology. In CoMSIA, five different similarity fields (electrostatic, hydrophobic [88-91], Steric, H-bond donor [92-96], and H-bond acceptor [97-100]) are correlated with biological activity. These fields were selected to cover major contributions to ligand binding.
In general, CoMSIA similarity indices AF,k between the compounds of interest is computed by placing a probe atom at the intersections of the lattice points using the following formula:
Where A is the similarity index at grid point q, summed over all atoms, i, of the fragment j under investigation.
Wprobe;k is the invetigated atom with a radius of 1 AË, charge +1, hydrophobicity +1, hydrogen bond donating +1, hydrogen bond accepting +1.
Wik is the actual value of physicochemical k property of atom i.
riq is the corelative distance between tne probe atom at grid poinr q and atom i of test molecule.
α is the attenuation factor with default value of 0.3.
- Razi R, et al. Naturally occurring enzyme inhibitors: A smart way to fight against micro-inflammation in human gut. Interdiscip J Microinflammation.2015;3:131.
- Franzén B, et al. Significance of diagnostic needle biopsy for the development of inflammation, tumour progression and metastasis. J MolBiomarkDiagn. 2016;S2:021
- Fabrègue F, et al. Association of inflammation and possible mild cognitive decline measured by the stroop cognitive function test. J Alzheimers Dis Parkinsonism.2016;6:237.
- Mohamed MSA. Role of genetic testing in lung transplantation; prediction of inflammation. J Genet Syndr Gene Ther. 2016;7:298.
- Sugama S, et al.Effect of chronic stress in the onset of Parkinson’s disease: Possible role of microglial cells in neuroinflammation. J NeurolDisord. 2015;S2:001.
- Gao WH, et al. The immunomodulatory effects of umbilical cord mesenchymal stem cell in critical limb ischemia patients. J Stem Cell Res Ther.2016;6:349.
- Ogura K, et al. A case of successful extracorporeal membrane oxygenation support for cardiac arrest associated with non-occlusive mesenteric ischemia. Emerg Med. 2016;6:322.
- Dai D, et al. EPCs-collagen sponge complex promotes neovascularization of chronic cerebral ischemia following multiple burr hole (MBH) surgery. J NeurolDisord.2016;4: 274.
- Pharmacophoremodeling and in silico screening for new kdr kinase inhibitors, bioorganic & medicinal chemistry letters
- Blum A and Arabi A.ChurgStrauss syndrome with migratory polyarthritis. J Clin Case Rep. 2014;4:405.
- Nuñez-Sotelo M, et al. Early inflammatory polyarthritis: Case study. RheumatolCurr Res. 2012;2:109.
- Pharmacophore and docking-based combined insilico study of KDR inhibitors. Journal of Molecular Graphics and Modelling
- Westin MCA, et al. Expression of VEGF-A in intraepithelial and invasive cervical neoplasia. J CytolHistol. 2015;S3:022.
- Bhaskari J andKrishnamoorthy L.impact of ascites and plasma levels of vegf-a in epithelial ovarian cancers. J Clin Cell Immunol.2015;6:353.
- Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking. Journal of Molecular Graphics and Modelling.
- Three–dimensional molecular field analysis of dihydro-indazolocarbazole analogues of KDR and tie–2 receptor tyrosine kinase inhibitors. Internet Electronic Journal of Molecular Design.
- Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors, Med Chem Res 18.
- 3D QSAR studies on a series of potent and high selective inhibitors for three kinases of RTK family. Journal of Molecular Graphics and Modelling.
- Vascular endothelial growth factor signaling pathways: Therapeutic perspective, molecular pathways.
- Vascular endothelial growth factor receptor-2: Structure, function, intracellular signalling and therapeutic inhibition, cellular signaling.
- Shankar VN,Lymphvasculogenesisand lymphangioma- an Update. J Cancer SciTher. 2011;3:149-153.
- Sarah MH and Abigail L.Lymphangiogenesis and its role in physiologic wound healing and the pathogenesis of pulmonary fibrosis. J Vasc Med Surg.2015;3:236.
- Francois M, et al. Ordered chaos: Harnessing developmental pathways in tumor-induced lymphangiogenesis. J Clin Cell Immunol.2014;5:270.
- Onuigbo WIB.Lymphangiogenesisin cancer: A review. Biochem Physiol.2014;3:138.
- Esmeryan KD. Detection of biological environments for endometrial stromal and mesenchymal stem cells growth through a quartz crystal microbalance based biosensor. Biosens J.2015;4:120.
- Shu B, et al. Notch1 signaling regulates wound healing via changing the characteristics of epidermal stem cells. J Stem Cell Res Ther.2016;6:348.
- Lin MR, et al.Hyaluronanelevates cell cycle regulators P130, E2F4 and P27kip1 in dormant human mesenchymal stem cells to regulate cell quiescence. J Stem Cell Res Ther. 2016;6:345.
- Prayitno A, et al.Tumoricidalactivation of macrophages using Jatrophacurcas leaf extract: As a proxy for the treatment of cancer. Immunome Res.2016;12:112.
- Arnold CE, et al Critical role for inflammatory macrophages in driving antigen-dependent th17 cell responses? J Cytokine Biol.2016;1:105.
- Kloc M, et al. Are macrophages responsible for cancer metastasis? J Immuno Biol.2016;1:103.
- Suresh A, et al. CART assignment of folding mechanisms to homodimers with known structures. J Proteomics Bioinform.2010;3:279-285.
- Shuo S, et al.Hemagglutininimmunoglobulin M (IgM) monoclonal antibody that neutralizes multiple clades of avian H5N1 influenza Avirus. J AntivirAntiretrovir.2009;1:051-055.
- Coscia MR. Antarctic fishIgT, a weird option of immunoglobulin genes. Immunogenet open access.2016;1:107.
- Krzysztof L, et al. IgGmonoclonal immunoglobulin (m-protein) as factor v inhibitor in multiple myeloma patient: Case report and discussion. J Clin Cell Immunol.2016;7:410.
- Shimizu T and Nakagawa K. Novel drug development of the next-generation T790M mutant specific epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small cell lung cancer. Biochem Anal Biochem.2016;5:258.
- Frezzato F, et al. Targeting bruton’s tyrosine kinase in chronic lymphocytic leukemia at the crossroad between intrinsic and extrinsic pro-survival signals. J Leuk.2016;4:207.
- Blaeser A, et al. Report: fourth international workshop for glycosylation defects in muscular dystrophies. J Genet Syndr Gene Ther.2016;7:286.
- Bousfield GR, et al. Comparison of follicle-stimulating hormone glycosylation microheterogenity by quantitative negative mode nano-electrospray mass spectrometry of peptide-n-glycanase-released oligosaccharides. J GlycomicsLipidomics.2015;4:129.
- Kumar M andBalajia PV. Diversity, abundance and distribution of o-linked glycosylation pathway enzymes in prokaryotes-a comparative genomics study. J GlycomicsLipidomics.2014;4:117.
- Sheng ZY, et al. The study of analytical identification on main monomer compounds of spoiled grass carp by high performance liquid chromatography of quadrupole time of flight mass spectrometry. J Food Process Technol.2016;7:600.
- Graft copolymerization of vinyl monomers onto chitosan:iii: graft copolymerization of acrylamide onto chitosan for antibacterial activity.
- Fragoso RL, et al.Genisteinproduces hepatoprotection through modulating egfr expression and phosphorylation in experimental fibrosis. J Liver.2016;5:196.
- Balbaa M. Protein phosphorylation. Biochem Physiol.2016;5:e147.
- Guterbaum TJ, et al. H2O2treatment of HUVECs facilitates PKC mediated Thr495 Phosphorylation on eNOS when Pre-treated with High Glucose Levels. J Metabolic Synd.2015;4:189.
- Castro A and Lorca T. Protein phosphatases triggering the dephosphorylation and inactivation of great wall. Single Cell Biol.2016;5:141.
- Daccache G andAllouche S. Recent advances towards understanding the role of opioid receptor phosphorylation. J ClinExpPathol.2016;6:264.
- Sun WL, et al. Acute cocaine differentially induces pka phosphorylation substrates in male and female rats. J Addict Res Ther. 2015;6:236.
- Colony forming unites - endothelial progenitor cells (CFU-EPCs) a surrogate marker for diabetic retinopathy and high cardiovascular mortality rate
- Kim HM, et al. Psychological factors associated with central serous chorioretinopathy. J PsycholPsychother. 2016;6:250.
- Geert ER, et al. Selection strategy of in vivo models for ophthalmic drug development in diabetic retinopathy. J Mol Genet Med. 2016;10:202.
- Agius LM. Putative status of actively operative performance attributes as determinants of minimal platform oncogenesis in c-myc amplification. Adv Cancer Prev.2016;1:108.
- Agius LM. Dimensions of cooperative cervical oncogenesis in abortive infection by human papillomavirus. Cervical Cancer.2016;1:109.
- Mbamalu ON, et al. HPLC determination of selected flavonoid glycosides and their corresponding aglycones in Sutherlandiafrutescensmaterials. Med Aromat Plants. 2016;5:246.
- Osman U and Gilbert CR. Bronchial necrosis following bevacizumab and stereotactic body radiotherapy for treatment of metastatic breast cancer. J PulmRespir Med. 2016;6:345.
- Salutari V andScambia G. Commentary on bevacizumab in ovarian cancer: Focus on clinical data and future perspectives. Trends GynecolOncol.2016;1:103.
- El-Fattah El-Shazly AA, et al. Therapeutic effects of extracts from Spirulinaplatensis versus bevacizumab on inflammation-associated corneal neovascularization. J Med SurgPathol.2016;1:102.
- Bahri S, et al. Initial experience of monitoring response of breast cancer to bevacizumab-containing chemotherapy using a new integrin specific pet imaging tracer [F-18]RGD-K5. J MolImag Dynamic.2015;5:116.
- Razavi GSE. Cancer treatment in the checkpoint inhibitor era. Immunome Res.2016;12:e105.
- Navin R and Kim SM. Therapeutic interventions using ursolic acid for cancer treatment. Med chem. 2016;6:339-344.
- Aurora kinase inhibitors in target specific cancer treatment.
- Schaafsma E, et al. Anticancer Activities of Resveratrol in Colorectal Cancer. Biol Med. 2016;8:317.
- Ichihara H, et al.Negativelycharged cell membranes-targeted highly selective chemotherapy with cationic hybrid liposomes against colorectal cancer in vitro andin vivo. J Carcinog Mutagen. 2016;7:267.
- Baran GK, et al. Colorectal cancer risk associated with reproductive factors among Turkish women.ReprodSyst Sex Disord.2016;5:174.
- Longo R, et al. A case report of choroidal metastasis from renal cell carcinoma during sunitinib treatment: a tumor “pharmacologic sanctuary”? J Clin Case Rep.2016;6:694.
- Karadimou A, et al. Pre-treatment status and changes in autoantibodies, lymphocytic populations, cytokines and vegf during sunitinib treatment of metastatic renal cell carcinoma (mRCC). Transl Med.2014;4:124.
- El Mesbahi O and El M'rabet FZ. Reversible hepatic cytolysis secondary to sunitinib in metastatic renal carcinoma. J Cancer SciTher. 2011;3:47-49
- Sampath KA, et al. Structural, magnetic and in vitro bioactivity of co-cu ferrite and bioglass composite for hyperthermia in bone tissue engineering. BioceramDev Appl.2016;6:091.
- Amin AMM, et al. Zirconia effect on the bioactivity and the mechanical properties of calcium magnesium silicate ceramics at (Cao+Mgo)/SiO2molar ratio close to unity. BioceramDev Appl.2016;6:088.
- Tanwar A, et al. Targeting antibiotic resistant Salmonella enterica: Bio-matrix based selection and bioactivity prediction of potential nutraceuticals. Biochem Anal Biochem.2015;4:217.
- Abrigach F andTouzani R.Pyrazolederivatives with NCN junction and their biological activity: A review. Med chem. 2016;6:292-298.
- Synthesis and chemical properties of new 3-aryl phosphacoumarin with potential biological activity
- Synthesis and biological activity of some 2,3- diphenylindole derivatives.
- Mishra S andGomase VS. Study of hydrophobicity and prediction of antigenic epitope of NADH dehydrogenase subunit 5 from d. medinensis. Drug Des. 2016;5:127.
- Mishra S andGomase VS. “Cytochrome B”- analysis of hydrophobicity, surface accessibility, antigenicity and prediction of MHC I and MHC II binders from dracunculiasis. Med chem. 2016;6:041-046.
- Mishra S andGomase VS.Study hydrophobicity and antigenicity of cytochrome c oxidase subunit ii fromD. medinensis: New prototype of synthetic vaccine development. ImmunochemImmunopathol.2016;2:113.
- Mishra S andGomase VS.study hydrophobicity and antigenicity of cytochrome c oxidase subunit ii from D. medinensis: New prototype of synthetic vaccine development. ImmunochemImmunopathol.2016;2:113.
- Ogunwolu L, et al. An optimized telecommunication system topology for expenditure minimization and improved spectral utilization efficiency. J TelecommunSyst Manage.2015;4:119.
- Ullah S and Wahid M. Topology control of wireless sensor network using quantum inspired genetic algorithm. Int J Swarm Intel EvolComput.2015;4:121.
- Woo EM, et al. Banded crystalline spherulites in polymers and organic compounds: interior lamellar structures correlating with top-surface topology. J AdvChem Eng. 2015;5:120.
- New innovation in renewable energy provided by the organic solar cells based on 3-aryl-4-hydroxyquinolin-2-(1H)-one. Correlation-Structure/electronic properties.
- Mekky ABH, et al. Effect of solvents on the electronic properties of fullerene based systems: Molecular modelling. J ApplComputat Math.2015;4:203.
- Zhou B and Xing C. Diverse molecular targets for chalcones with varied bioactivities. Med chem.2015;5:388-404.
- Dallas DC, et al.Couplingmass spectrometry-based “omics” sciences with bioguided processing to unravel milk’s hidden bioactivities. Adv Dairy Res.2013;1:104.
- Mishra S andGomase VS. Study of hydrophobicity and prediction of antigenic epitope of NADH dehydrogenase subunit 5 from D. medinensis. Drug Des.2016;5:127.
- Mishra S andGomase VS. “Cytochrome B”- Analysis of hydrophobicity, surface accessibility, antigenicity and prediction of MHC I and MHC II binders from dracunculiasis. Med chem.2016;6:041-046.
- Oda S. Relationship between interfacial hydrophobicity and hydroxylation activity of fungal cells located on an organic–aqueous interface. Ferment Technol.2015;4:e122.
- Qiao G, et al. Modified a colony forming unit microbial adherence to hydrocarbons assay and evaluated cell surface hydrophobicity and biofilm production of Vibrio scophthalmi. J BacteriolParasitol.2012;3:130.
- Mishra S and Gomase VS. Study of hydrophobicity and prediction of antigenic epitope of NADH dehydrogenase subunit 5 from D. medinensis. Drug Des.2016;5:127.
- Mishra S andGomase VS. “Cytochrome B”- analysis of hydrophobicity, surface accessibility, antigenicity and prediction of MHC I and MHC II binders from dracunculiasis. Med chem.2016;6:041-046.
- Fialová S, et al. Experimental verification of the use of ultra-hydrophobic materials for water aeration. Int J Adv Technol.2015;6:147.
- Mishra S andGomase VS. “Cytochrome B”- analysis of hydrophobicity, surface accessibility, antigenicity and prediction of MHC I and MHC II binders from dracunculiasis. Med chem.2016;6:041-046.
- Zhang CJ, et al. Synthesis and physicochemical properties of two-dimensional gallium sulfide crystals. Bioenergetics.2016;5:221.
- Smichi N, et al. Physicochemical characterization and nutritional quality of fish by-products: In vitro oils digestibility and synthesis of flavour esters. J Food Process Technol.2016;7:602.
- Dagadkhair AC, et al. Effect of storage on physicochemical properties of spiced fish sauce. J Nutr Food Sci.2016;6:520.
- Dagadkhair AC, et al. Effect of storage on physicochemical properties of spiced fish sauce. J Nutr Food Sci. 2016;6:520.
- Chebbi S, et al. Physicochemical characterization and kinetic study of flotation process applied to the treatment of produced water. J Environ Anal Toxicol.2016;6:362.
- Pharmacophore and docking-based combined insilico study of KDR inhibitors,
- Westin MCA, et al. Expression of VEGF-A in intraepithelial and invasive cervical neoplasia. jcytolhistol.2015;S3:022.
- Bhaskari J andKrishnamoorthy L.Impact of ascites and plasma levels of VEGF-A in epithelial ovarian cancers. J Clin Cell Immunol.2015;6:353.
- Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking.