International Journal of Drug Discovery

11-16

Authors: Koteswara Reddy G., Mohan Kalyan Reddy K., Nagamalleswara Rao K., Gyana R.Satpathy

The bacteria Clostridium botulinum causing botulism. Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium botulinum.CDP-diacylglycerol-serine O-phosphatidyltransferase is an enzyme that catalyzes the CDP-diacylglycerol, L-serine and produce Cytidine monophosphate (CMP), (3-snphosphatidyl)- L-serine in Clostridium botulinum. CMP is a nucleotide that is helpful in RNA synthesis in Clostridium botulinum.The objective of enzyme inhibition needs structural characterization from its 3-D structure in rational structure based drug design. Homology modeling can produce high-quality structural models when the target and templates are closely related. MODELLER is the program used for homology modeling which provides accurate and efficient models to build loops and side chains found non-identical in sequence. It implements comparative protein structure modeling by satisfaction of spatial restraints. The stereo chemical quality of a best model is validated by PROCHECK server with 86.2% residues under favored region from Ramachandran plot. The CASTp is used for locating, delineating and measuring concave surface regions on three-dimensional structures of proteins. The residues are identified in burial cavity of the best model as Leu (131,141,156), Ala (132), Ile (138,142), Asn (145), Thr (149,153), and Gly (151) with hydrophobic nature. These include pocket located on protein surfaces and voids buried in the interior of proteins that are frequently associated with binding events. Thus present studies of modeling of CDP-diacylglycerol-serine O-phosphatidyltransferas enzyme has brought future prospective to fight against botulism disease and provide better health standaaards for community.

20-50

Authors: Kranthi Raj K., Pathak L.P., Muttineni Ravikumar, Ramachandrana D.

Leukotriene A4 hydrolase (LTA4H) is a hydrolase with a bifunctional zinc enzyme, which plays a role in inflammation. LTA4H may also play an important role in carcinogenesis, especially chronic inflammation-associated carcinogenesis. In this study, chemical feature based pharmacophore models based on 22 currently available LTA4H inhibitors have been developed with the aid of HipHop and HypoRefine modules within Catalyst program package. 3D pharmacophore model developed was, characterized by distinct chemical features such as Hydrogen-bond acceptor (HA), Hydrogen-bond donor (HD), Hydrophobic aliphatic (HPAli), Hydrophobic aromatic (HPAr) that are found to be responsible for the activity of the LTA4H inhibitors. The correlation coefficient, root mean square deviation and cost difference were 0.92, 1.0867 and 53.62 respectively, suggesting that a highly predictive pharmacophore model was successfully obtained. The results of our study provide a valuable tool in designing new leads with desired biological activity for virtual screening.

8-16

Authors: Chinna Gangadhar B., Shyam Sunder R., Vimal Kumar Varma. M., Sleeva Raju M., Sai Kiran M.

Purpose: The aim of this study was to formulate and evaluate microspheres as controlled release preparations of a highly water-insoluble drug, Indomethacin, using natural polymer, Egg albumin; semi synthetic polymer, Ethyl cellulose and Synthetic polymer, Meth acrylic acid esters (Eudragit L 100) as the retardant materials. Methods: Microspheres were prepared by solvent evaporation method using an acetone / liquid paraffin system and Phase separation co-acervation method using petroleum ether and coconut oil as dispersion and continuous phase systems. Magnesium stearate was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were evaluated for their micromeritic properties, drug content and encapsulation efficiency and characterized by Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The in vitro release studies was performed by buffer change method to mimic Gas Intestine Tract(GIT) environment in pH 1.2, carbonate buffer (acidic) and pH 7.4, phosphate buffer (Alkaline). Results: The prepared microspheres were pale yellow, free flowing and spherical in shape. The mean particle size of the microspheres was found in the range of 150 to 400μm. The drug-loaded microspheres showed 70-86% of entrapment and release was extended up to 6 to 8 h releasing 86% of the total drug from the microspheres. The infrared spectra showed stable character of Indomethacin in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. Scanning electron microscopy study revealed that the microspheres were spherical and porous in nature. Conclusion: The best-fit release kinetics was achieved with Koresmeyer-Peppas plot followed by zero order and First order. The release of Indomethacin was influenced by the drug to polymer ratio and particle size & was found to be both diffusion and dissolution controlled.

5-9

Authors: Girish Gupta, Nikhil Gupta, Mayank Gupta, Soham Trivedi, Prasad Patil, Vamsi Krishna K, Hipal Gaudani, Gomase V.S.

Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies and has the potential to revolutionize clinical practice, including cancer diagnosis. Oncoproteomics screening based on proteomic platforms as a complement to histopathology, individualized selection of therapeutic combinations that target the entire cancer-specific protein network, real-time assessment of therapeutic efficacy and toxicity and rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance. Oncoproteomics refers to the application of proteomic technologies in oncology and parallels the related field of oncogenomics. The challenges ahead and perspectives of oncoproteomics for biomarkers development are also addressed. With a wealth of information that can be applied to a broad spectrum of biomarker research projects serves as a reference for biomarker researchers, scientists working in proteomics and bioinformatics, oncologists, pharmaceutical scientists, biochemists, biologists, and chemists.

18-27

Authors: Thikekar V.P., Sawant J.J., More M.K., Nair V.K., Athalekar P., Patil D., Kulkarni S., Gomase V.S.

This article reviews the available literature on the regulation of miRNA processing that occurs within normal cells and embryonic stem cells, during development or in diseases such as cancer. Also, explains miRNA biogenesis process for which regulation occurs. RNA editing of miRNA precursors, regulation by RNA binding proteins, alterations in the levels of key processing proteins, as well as a number of unknown mechanisms contribute to the regulation of miRNA processing as well as miRNA expression pattern during adipogenesis.

34-39

Authors: Meshram R.J., Jangle S.N.

Neuraminidase (NA) is the enzyme coded by Influenza-A virus genome that catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. It cleaves off the terminal sialic acids on the glycosylated NA during virus budding to facilitate virus release, making it most important target for designing drug against Flu. Recently cases are reported of Influenza virus becoming resistant to NA inhibitors like Oseltamivir. The outbreak of Swine flu and its resistance to oseltamivir is suspected to be caused due to mutation H274Y in the enzyme neuraminidase of H1N1 strain of influenza virus. This work involved active site analysis, molecular docking and binding energy studies on NA that demonstrate the conformational changes in active site which might result in increase in binding energy of oseltamivir when it is mutated as H274Y.

52-55

Authors: Singh S., Bishnoi A., Awasthi R., Pandey V.K., Tiwari A.K., Awasthi N.K., Srivastava K.

Reaction of anthranilic acid with an excess equivalent of benzoyl chloride in dry pyridine afforded 2- phenyl- 4H- benzo [d] [1, 3] oxazin- 4- one (I) which on reaction with
-aminoethanol (cholamine) in pyridine solvent yielded 3- (2- hydroxyethyl) - 2- phenylquinazolin- 4(3H)- one (II). When (II) was reacted with 8-hydroxyquinoline (oxine) in conc. H2SO4, 3- [2- (8- hydroxy- quinolin- 5- yl) ethyl] 2- phenylquinazolin - 4(3H)- one (III) was obtained which on reaction with primary aromatic amines and excess of aromatic aldehydes furnished 3- [2- (3- benzoyl- 2, 4- diphenyl- 3, 4- dihydro- 2H- [1, 3] oxazino [5, 6-h] quinazolin- 6- yl) ethyl- 2- phenyl- quinazolin -H(3H)- ones (IV). The target compounds (IV) and the intermediates (III) were evaluated for their antihyperglycemic activity in sucrose loaded rat models.

10-13

Authors: Gomase V.S., Phadnis A.C., Waghmare Somnath

Scorpion venom is an antigenic, water-soluble, heterogenous mixture. The Na+-channel specific toxins from scorpions are modifiers of the channel gating mechanism. The recombinant DNA vaccines involved targeting multiple antigenic components to direct and empower the immune system to protect the host from infection. Limitation of therapy to the treatment of patients suffering from various adverse reaction and contraindications are always experienced. Antigenic epitope on iberiotoxin - eastern Indian scorpion are important determinant of protection against spider venom. As our knowledge of the immune responses to a protein antigen progressed, it became clear that the whole protein is not necessary for raising the immune response, but small segments (DVDCSVSKECWSVCKDLFG; 4-22) of protein called the antigenic determinant or the epitope is sufficient for eliciting the desired immune response. In analysis predicted antigenic epitope iberiotoxin protein is seen. Antigenic epitope from iberiotoxin is a predicted immunization strategy against various diseases.

18-20

Authors: Gomase V.S., Shankar S., Gangawane A.K., Sherkhane A.S.

The toxin LTx5 toxin is an 116aa residue peptide is isolated from the venom of Lasiodora sp. IBSP8539.In this assay we have predicted the binding affinity of toxin LTx5 toxin having 116 amino acids, which shows 109 nonamers. Peptide fragments of the neurotoxin can be used to select nonamers for use in rational vaccine design and to increase the understanding of roles of the immune system in neurotoxin studies. Small segment ‘3- STFIIMISLAVALATWPSEH-22’ of toxin protein called the antigenic epitopes is sufficient for eliciting the desired immune response. Immunization cassettes should be capable of immunizing of broad immunity against both humoral and cellular epitope thus giving vaccines the maximum ability to deal with neurotoxin protein of Eurypelma californicum. Binding ability prediction of antigen peptides to MHC class molecules is important in vaccine development, We also found the SVM based MHCII-IAb peptide regions, 40- YALADRAEK, 10- ISLAVALAT, 99- MYQAERALE, 14- VALATWPSE, (optimal score is 1.494); MHCII-IAd peptide regions, 96- LDIMYQAER, 29- SETKLNVEL, 68- GASVLCEAV, 4- STFIIMISL, (optimal score is 0.604); MHCII-IAg7 peptide regions , 38- GPYALADRA, 98- IMYQAERAL, 9- MISLAVALA, 99- MYQAERALE, (optimal score is 1.904); and MHCII- RT1.B peptide regions, 17- ATWPSEHIE, 101- QAERALEKL, 98- IMYQAERAL, 108- KLASSFRCE, (optimal score is 0.601) which represented predicted binders from neurotoxin protein. We have predicted a successful immunization.