Vol.50 Issue No.02 FEBRUARY 2013 INDIAN DRUGS 50(02) FEBRUARY 2013 1 2 INDIAN DRUGS 50(02) FEBRUARY 2013 Vol. 50 No. 02 February 2013 REVIEW ARTICLE - Protease Inhibitors: A Review Sapkale P. V., Jadhav S. B. and Sable P. N. ................................................................. 5 ORIGINAL RESEARCH ARTICLES - Method Development and Validation of Olanzapine in Pure and Pharmaceutical Dosage form by RP-HPLC Method Mastiholimath V.S., Dandagi P.M., Gadad A.P., Murali Krishna N.V. and Mannur V. .............................................................................................................. 20 - Quantitative Determination of Deferasirox in Bulk and Pharmaceutical Formulation by UV Spectrophotometric Method Marathe G. M., Pande V. V., Patil P. H., Mutha R. E. and Bari S. B. ........................... 27 - Preclinical Evaluation of Nootropic Activity of Glabridin Rich Extract of Glycyrrhiza Glabra using Passive Avoidance Paradigm in Rats Desai S. K., Pandey C. H. and Mulgaonkar S.M. ......................................................... 33 - Antihyperglycemic and In Vitro Antioxidant Activities of Punica Granatum Linn. in Alloxan Induced Diabetic Rats Patil U. S., Bandawane D. D., Bibave K. H. and Chaudhari P. D. ................................ 39 SHORT NOTES - A Novel Method For Isolation of Mangiferin from Mangifera Indica L. Bark Gholkar M. S and Laddha K. S. ................................................................................... 47 - Anti-Inflammatory Effect of Seeds ofTamarindus Indica in Wistar Rats Hivrale M. G., Mali A. A. and Bandawane D. D. ........................................................... 49 INDIAN DRUG MANUFACTURERS' ASSOCIATION 102-B, 'A-Wing', Poonam Chambers, Dr. A.B. Road, Worli, Mumbai - 400 018 Tel : 022-2494 4624 / 2497 4308 Fax: 022-2495 0723 E-mail: [email protected] / [email protected], Website: www.idma-assn.org INDIAN DRUGS 50(02) FEBRUARY 2013 3 Founder Editor *Dr. A. Patani, D.Sc. (Germany) EDITORIAL COMMITTEE Editor Dr. Gopakumar G. Nair, Ph.D. Associate Editors Mr. J. L. Sipahimalani, B. Pharm. Hons. (London), MRCS, FRPharmS Dr. Nagaraj Rao, D.Sc. (Germany) Dr. George Patani, Ph.D. Consulting Editor Dr. S. G. Deshpande, M.Sc. (Tech.), Ph.D. Editorial Board Editorial Advisory Board Prof. K. G. Akamanchi, Ph.D. (Tech.) Prof. Y. K. Agrawal, Ph.D., F.I.C., F.R.M.S. Dr. Evans Coutinho, Ph.D. (Tech.) Prof. H. L. Bhalla, Ph.D. Prof. Padma Devarajan, M.Pharm., Ph.D. (Tech.) Dr. B. N. Dhawan, M.D. Dr. Prashant M. Dikshit, Ph.D. Prof. S. S. Handa, Ph.D. Prof. A. K. Gadad, M.Pharm., Ph.D. Dr. C. I. Jolly, Ph.D. Dr. K. N. Ganesh, Ph.D. Dr. C. L. Kaul, Ph.D. Dr. (Mrs.) Gopa Ghosh, Ph.D. Dr. S. P. S. Khanuja, Ph.D. Dr. Parthajyoti Gogoi, Ph.D. Prof. J. K. Lalla, Ph.D. Dr. Nirmala D. Grampurohit, Ph.D. Dr. D. B. Anantha Narayana, Ph.D. Dr. (Mrs.) S. S. Mahajan, M.Sc. (Tech.), Ph.D. Dr. Nitya Anand, Ph.D. Prof. Bhushan Patwardhan, Ph.D. Dr. Harish Padh, Ph.D. Dr. Ashwinikumar Raut, M.D. Dr. M. K. Raina, Ph.D. Dr. Sanjay Singh, M.Pharm, Ph. D. Dr. A. V. Rama Rao, Ph.D. (Tech.), D.Sc. Prof. Saranjit Singh, M.Pharm., Ph.D. Dr. G. N. Singh, M.Pharm., Ph.D. Prof. N. Udupa, M.Pharm., Ph.D. Prof. R.T. Sane, Ph.D. Dr. K. Valliappan, M.Pharm., Ph.D. Prof. M. N. Saraf, M.Pharm., Ph.D. Dr. A. A. Natu, Ph.D. Dr. P. D. Sethi, Ph.D. Dr. N. G. N. Swamy, Ph.D. Dr. Ashok Vaidya, M.D., Ph.D., F.A.I.M. Dr. J. S. Yadav, Ph.D., FNA 4 INDIAN DRUGS 50(02) FEBRUARY 2013 REVIEW ARTICLE PROTEASE INHIBITORS : A REVIEW Sapkale P. V., Jadhav S. B*. and Sable P. N. (Received 29 August 2012) (Accepted 19 December 2012) ABSTRACT HIV protease inhibitors were first invented between 1989 and 1994 by researchers working for the pharmaceutical companies of Hoffmann- La Roche Inc. (in Nutley, New Jersey), Abbott Laboratories and Merck & Co., Inc. HIV protease inhibitors are used in the treatment of patients with AIDS and were considered the first breakthrough in over a decade of AIDS research. Currently, there are five HIV protease inhibitors approved by FDA for the treatment of HIV infection. These drugs work at the final stage of viral replication and attempt to prevent HIV from making new copies of itself by interfering with the HIV protease enzyme. As a result, the new copies of HIV are not able to infect new cells. Occurrence of protease along with structural properties, classification of inhibitors like Saquinavir, Ritonavir, Indinavir, Nelfinavir etc and life cycle of virus confirm the role of protease inhibitor. Other parameters like adverse effect, application, structure activity relationship and dose regime shows need of medication for person suffering from HIV virus. Keywords: Viral replication, Enzyme, Lifecycle, • Metalloproteases Structural properties, Adverse reaction. • Glutamic acid proteases INTRODUCTION The threonine and glutamic-acid proteases were not described until 1995 and 2004, respectively. The Protease mechanism used to cleave a peptide bond involves A protease (also termed peptidase or proteinase) making an amino acid residue that has the cysteine is any enzyme that conducts proteolysis, that is, begins and threonine (proteases) or a water molecule protein catabolism by hydrolysis of the peptide bonds (aspartic acid, metallo- and glutamic acid proteases) that link amino acids together in the polypeptide chain nucleophilic so that it can attack the peptide carboxyl forming the protein. group. One way to make a nucleophile is by a catalytic triad, where a histidine residue is used to activate Classification of Protease serine, cysteine, or threonine as a nucleophile. Within Proteases are currently classified into six broad each of the broad groups proteases have been groups: classified, by Rawlings and Barrett, into families of related proteases. For example, within the serine • Serine proteases proteases families are labelled Sx where S denotes • Threonine proteases the serine catalytic type and the ‘x’ denotes the number • Cysteine proteases of the family, for example S1 (chymotrypsins). An up to date classification of proteases into families is • Aspartate proteases found in the MEROPS database 1, 2. *For correspondence Occurrence of protease Modern College of Pharmacy, Sector 21 Yamuna Nagar, Nigdi, Pune-411044. Proteases occur naturally in all organisms. These E-mail: [email protected] enzymes are involved in a multitude of physiological INDIAN DRUGS 50(02) FEBRUARY 2013 5 reactions from simple digestion of food proteins to Proteases are divided into four major groups highly regulated cascades (e.g., the blood-clotting according to the character of their catalytic active cascade, the complement system, apoptosis site and conditions of action: serine proteinases, pathways, and the invertebrate prophenoloxidase- cysteine (thiol) proteinases, aspartic proteinases, and activating cascade). Proteases can either break metallo proteinases. Attachment of a protease to a specific peptide bonds limited( proteolysis), depending certain group depends on the structure of catalytic on the amino acid sequence of a protein, or break site and the amino acid (as one of the constituents) down a complete peptide to amino acids (unlimited essential for its activity. Proteases are used throughout proteolysis). The activity can be a destructive change, an organism for various metabolic processes. Acid abolishing a protein’s function or digesting it to its proteases secreted into the stomach (such as pepsin) principal components; it can be an activation of a and serine proteases present in duodenum (trypsin function, or it can be a signal in a signaling pathway. and chymotrypsin) enable us to digest the protein in Bacteria also secrete proteases to hydrolyze (digest) food; proteases present in blood serum (thrombin, the peptide bonds in proteins and therefore break plasmin, Hageman factor, etc.) play an important role the proteins down into their constituent monomers. in blood-clotting, as well as lysis of the clots, and the Bacterial and fungal proteases are particularly correct action of the immune system. Other proteases important to the global carbon and nitrogen cycles in are present in leukocytes (elastase, cathepsin G) the recycling of proteins, and such activity tends to be and play several different roles in metabolic control. regulated by nutritional signals in these organisms. Proteases determine the lifetime of other proteins The net impact of nutritional regulation of protease playing important physiological role like hormones, activity among the thousands of species present antibodies, or other enzymes; this is one of the in soil can be observed at the overall microbial fastest “switching on” and “switching off” regulatory community level as proteins are broken down in mechanisms in the physiology of an organism. By response to carbon, nitrogen, or sulfur limitation. complex cooperative action the proteases may A secreted bacterial protease may also act as an proceed as cascade reactions, which result in rapid exotoxin, and be an example of a virulence factor in and efficient amplification of an organism’s response bacterial pathogenesis. Bacterial exotoxic proteases to a physiological signal. Proteases are part of many destroy extracellular structures. Protease enzymes laundry detergents5. are also used extensively in the bread industry as bread improver3. Protease Inhibitors Protease inhibitors are a class of drugs used to Proteases, also known as proteinases or treat or prevent infection by viruses, including HIV proteolytic enzymes, are a large group of enzymes.