Immunology “Toxicological studies on Snake Venom specific antibodies (IgY) from Chicken egg”
Brief Synopsis: In recent years, IgY antibodies produced in chicken egg are being explored as an alternative to mammalian antibodies for diagnostic and therapeutic use. Leghorn chickens were injected with a sub-lethal dose of venom of the poisonous snake, Echis carinatus (Kraits). The antibodies were purified from the egg yolks of immunized birds by a combination of water dilution method followed by salt fractionation. The efficiency of these antibodies in protecting mice against the lethal effects of the venom has been demonstrated by in vitro neutralization of snake venom in mice. Since there are no studies on the biosafety of IgY antibodies which have great potential for therapeutic use, comprehensive toxicological studies viza acute oral, intraperiotneal, intramuscular, mucous membrance irritation potential, 28-day repeated intraperitoneal as well as allergenicity and mutagenicity evalution were carried out. These studies revealed that therapeutic IgY antibodies could be safely used for evaluation in human trials.
Publications published: Journal of Cell and Tissue Research
Author: Manjula J. Kusum.P, Sairam A.K, Murthy P.B. & Subbarao .P.V.
May 10 2006
Chemistry : Synthesis of isonicotinylhydrazones from anarcardic acid and their in vitro activity against Mycobacterium smegmatis
Brief Synopsis: Isonicotinylhydrazones were synthesized from a natural product anacardic acid, a major constituent of cashew nut shell liquid. The unsaturated side chain in anacardic acid and its 5-nitro derivative were converted into C8-aldehydes by oxidative cleavage. C8 –aldehydes are then coupled with isoniazid (an anti-TB Drug) to obtain N-isonicotinoyl – N’-8-[(2’-carbohydroxy—3’-hydroxy) phenyl]octanal hydrazone (5) and N-isonicotinoyl-N’-8-[(2’-carbohydroxy-3’-hydroxy-6-nitro) phenyl]octanal hydrazone(6). These isonicotinoyldhydrazones of anacardic aldehydes showed potent antimycobactrial activity against Mycobacterium smegmatis mc2155. The synergistic studies of 5 and 6 with isoniazid showed more inhibitory activities than isoniazid alone. Compounds 5 and 6 also showed activity against mycobacterium tuberculosis H37Rv.
Publications published: European Journal of Medicinal Chemistry
Author: B.NarayanaSwamy, T.K.Suma, G.Venkateswara Rao & G.Chandrasekara Reddy.
15 November 2006
Chemistry: One pot conversion of 2-nitrobenzonitriles to quinazoline-4(3H)-ones and synthesis of gefitinib and erlotinib HCl
Brief Synopsis: A simple and efficient one-pot conversion of 2-nitrobenzonitriles to quinzolin-4(3H)-ones involving reduction, formylation, hydrolysis and cyclization is reported. These quinazolionones have been used for making in economical way the anticancer drug molecules gefitinib (Iressa®) and erlotinib HCL (Tarceva®).
Publications published: Heterocycles
Author: B.V.Chandregowda, G.Venkateswara Rao and G.Chandrasekara Reddy
17 November 2006
Chemistry: Improved synthesis of Gefitinib and Erlotinib HCl- anticancer agents
Brief Synopsis: A highly efficient and commericlaly viable process for the synthesis of 6, 7 dihydroxy-4-anilinoquinazolin derivatives gefitinib (1) and erlotinib hydrochloride (2) used for the treatment of non-small cell lung cancer (NSCLC) pancreatic cancer, is reported. This new process has improved yields and avoids the unstable 4-chloroquinazline intermediate. The intermediates and final products were characterized by 1H and 13C nuclear magnetic resonance (NMR), mass spectra (MS) and 3elemental analysis, and purities of final products were determined by high performance liquid chromatogram (HPLC) and potentiometric titration methods.
Publications published: Synthetic Communications
Author: V.Chandregowda, G.Venkateswara Rao and G.Chandrasekara Reddy
5 February, 2007
Chemistry: Convergent approach for commercial synthesis of Gefitinib and Erlotinib HCl
Brief Synopsis: Abstract: An efficient, economical and large-scale convergent synthesis of epidermal growth factor receptor- tyrosine kinase inhibitors gefitinib (1, Iressa®) and erlotinib (2, Tarceva®) approved by US FDA for the treatment of non-small-cell lung cancer is described. The formation of 4-anilinoquinazolines are achieved in a simple one-pot reaction of suitable formamidine intermediates and substituted anilines involving Dimroth rearrangement there by avoiding the need to make quinazolin-4(3H)-one intermediates which require a large experimental inputs. Using this process, we have produced drug candidates 1 with overall yield of 66% from 4-methoxy-5-[3-(4-morpholinyl) propoxy]-2-nitrobenzonitrile (3) and 2 with 63% from 4,5-bis-(2-methoxyethoxy)-2-nitrobenzonitrile (6) on multigram scale.
Publications published: Organic Process Research and Development(most accessed article)
Author: V.Chandregowda, G.Venkateswara Rao and G.Chandrasekara Reddy
24 July , 2007
Chemistry: Garcinia Lactone
Brief Synopsis: The title compound, C6H6O7 garcinia lactone [Systematic name: (2S, 3S)-3-hydroxy-5-oxo-2,3,4,5-tetrahydrofouran-2,3-dicarboxylic acid]was isolated from the rind of Garcinia cambogia. The five membered ring adopts an envelope conformation and the packing is stabilized by O-H-O and C-H-o interactions.
Publications published: Acta Crystallographica Section
Author: Sudharshan Mahapatra, Srijita Basu Mallik, G. Venkateshwara Rao, G. Chandrasekara Reeddy and T.N Guru Row
4 August 2007
Synthesis of benzamide derivatives of anacardic acid and their cytotoxic activity
Brief Synopsis: TSynthesis of benzamide derivatives of anacardic acid and their cytotoxic activity
Publications published: European Journal of Med chemistry
Author: Venkateshappa Chandregowda, Anil Kush, Goukanapappli Chandrasekhara Reddy
Plant Defense- Thrips – tospovirus interactions: Biological and molecular implications
Brief Synopsis: The occurrence of thrips vectors in considerable numbers enables their functioning in a dual role as a vector and as direct crops pests. The resistance of thrips to pesticides has enabled quick transmission of viruses, the transient nature of their populations being essentially responsible for the infection. The feeding behavior of thrips contributes in a large measure towards their ability to act as vectors, enabling leaf-to-leaf transmission of the tospoviruses. The specific association of the tospoviruses and thrips vectors, particularly relating to the molecular profiles, needs increasing scrutiny to come to proper conclusion. A better understanding to of the nature of virus multiplication and the pathways leading to their entry into the salivary glands and the ability of the second instar larvae to inoculate plants need further inputs. The intraspecific diversity of thrips vectors as a result of population studies from various parts of the country, would further enable a better understanding of the ability each species to transfer the virus, besides the better appreciation of the chemical ecology of thrips – host-plant interaction, not to mention the relevance of serodiagnosis in detecting disease or health.
Publications published: Current Science
Author: Prof. T.N. Ananthakrishnan, Dr. R.S. Annadurai
25th April 2007
Drugs Screening Systems: Actin cytoskeleton as a putative target of the neem limonoid Azadirachtin
Brief Synopsis: Limonoids isolated from the Indian neem tree (Azadirachta indica) have been gaining global acceptance in agricultural applications and in contemporary medicine for their myriad but discrete properties. However, their mode of action is still not very well understood. We have studied the mode of action of Azadirachtin A, the major limonoid of neem seed extracts, using Drosophila melanogaster as the model system. Azadirachtin A induces moderate-to-severe phenotypes in different tissues in a dose-dependent manner. At the cellular level, Azadirachtin A induces depolymerization of Actin leading to arrest of cells and subsequently apoptosis in a caspase-independent manner. Azadirachtin A-induced phenotypes were rescued by the over-expression of Cyclin E in a tissue-dependent manner. Cyclin E, which caused global rescue of Azadirachtin A-induced phenotypes, also effected rearrangement of the actin filaments. These results suggest that probably actin is a target of Azadirachtin A activity.
Publications published: Journal : Insect Biochemistry and Molecular Biology
Author: Aritakula Anuradha, Ramasamy S. Annadurai, L.S. Shashidhara
8 March 2007
Chemistry “Synthesis of 2-(N-disubstituted amino) ethyltriphenylphosphonium bromide “
Brief Synopsis: 2-(N-Disubstituted amino)ethytriphenylphosphonium bromides are prepared in quantitative yields with high purity by reacting secondary amines with 2-methoxyethyltriphenylphosphonium bromide under aqueous conditions. The differential reactivity of this reagent offers advantages for the preparation of aminoethyltriphenylphosphonium bromides possessing nulclophiles such as hydroxyl groups.
Publications published: Tetrahedron Letters
Author: G. Venkateshwara Rao, G. Chandrasekhara Reddy
4 December 2007
" Drugs Screening and Systems Title: In silico approach of azadirachtin binding with actins “
Brief Synopsis: In silico docking analysis reported here suggests that insect cellular cytoskeletal b-actin could be the target of Azadirachtin A (Aza— the principle bioactive compound of neem seeds). The best docking energy of _40.09 kcal/mol at 8.73A ° RMSD and predicted hydrogen bond between Arg210 and carboxymethyl group of Aza accompanied with seven hydrophobic interactions in the proposed binding site strongly support this hypothesis. This is of specific interest due to the non-affinity of Aza to mammalian b-actins under the same set of conditions, although b-actins across the species are highly conserved. Our results show that few scattered amino acid changes have caused significant steric hindrance in the binding pocket for mammalian b-actin, causing a reverse orientation of Aza. These resultssuggest a model to support the recently observed biological effects caused by Aza in Drosophila cytoskeletal elements and explain why Aza is highly specific to insects than mammals.
Publications published: Journal: Insect Biochemistry and Molecular Biology
Author: R. Pravin Kumar, M.N Manoj, Anil Kush, R.S. Annadurai
8 March 2007
Drosophila genetics Biochemical and molecular evidence o azadirachtin binding to insect actins