SYNTHESIS OF NOVEL PYARAZOLIDINEDIONE SUBSTITUTED - Download as DOC by 9c01PDQ

VIEWS: 0 PAGES: 15

									SYNTHESIS AND BIOLOGICAL EVALUATION OF
 NOVEL PYRIMIDO-DIAZEPINE DERIVATIVES



                SYNOPSIS FOR
            M.PHARM DISSERTATION




                SUBMITTED TO

   RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
            BANGALORE, KARNATAKA




                      BY

        KALABANDI VENKATACHALAPATHI

             I M.PHARM (2011-2012)

   DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

      M.S. RAMAIAH COLLEGE OF PHARMACY

              BANGALORE-560054




                       1
     RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
               BANGALORE, KARNATAKA

                       ANNEXURE II

       PROFORMA FOR REGISTRATION OF SUBJECT
                FOR DISSERTATION


1. NAME OF THE            KALABANDI
   CANDIDATE AND          VENKATACHALAPATHI,
   ADDRESS                S\o K.V.S.SASTRY,MF-35/2,
                          SYNDICATE BANK OFFICERS
                          QUARTERS,
                          NANDINI LAYOUT,
                          BANGALORE-560096.

2. NAME OF INSTITUTION    M.S.RAMAIAH COLLEGE OF
                          PHARMACY,
                          M.S.R.I.T Post, M.S.R Nagar, Bangalore
                          560 054

3. COURSE OF THE STUDY    M.PHARM
   AND SUBJECT            PHARMACEUTICAL CHEMISTRY



4. DATE OF ADMISSION      05/07/2011



                   TITLE OF THE TOPIC
     SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL
5.          PYRIMIDO-DIAZEPINE DERIVATIVES




                            2
6. BRIEF RESUME OF THE INTENDED WORK

6.1 NEED FOR THE STUDY

      A broad use of antibiotics has been followed by emergence of resistance. There has
  been increase in number of newer microbial diseases which are gaining more
  importance due to their wide spread occurrence. The problem of controlling infectious
  diseases and role of modern medicinal chemist in this effect is steadily increasing.
  There has been valuable consideration and interest in the discovery of novel
  compounds with enhanced antimicrobial activity and with fewer side effects.
      Recently there has been considerable interest in discovery of chemotherapeutic
  agents against neoplastic diseases.
      Heterocyclic compounds containing the pyrimidine nucleus possess a diversity of
  useful biological effects. As pyrimidine is a basic nucleus in DNA and RNA, it has
  been found to be associated with diverse biological activities. Pyrimidine and their
  derivatives possess several interesting biological activities such as antimicrobial1-5,
  antitumor 2, 6 and anticonvulsant activities7, 8.
       The diazepine nucleus is a pharmacophoric scaffold and represents a class of
  heterocycles with a wide range of biological applications such as anticonvulsant,
  antianxiety and neuroleptic agents. Some heterocyclic compounds containing diazepine
  moieties were reported to possess antimicrobial9-13 and antitumor activity14.
     There are reports of some pyrimido-diazepine derivatives showing antitumor
  activity15-20.
     Hence, the objective of the current work is to synthesize some novel compounds
  having both pyrimidine as well as diazepine moieties and screen for antimicrobial and
  in-vitro antitumor activity.




                                               3
6.2 REVIEW OF LITERATURE:

     Studies on synthesis of pyrimidine derivatives and their pharmacological evaluation
      were reported1.

     Synthesis, antibacterial and anticancer evaluation of some pyrimidine derivatives
      were reported2.

     Synthesis and antimicrobial activity of linked heterocyclics containing pyrazole-
      pyrimidine rings were reported3.

     Synthesis of novel pyrimidine and fused pyrimidine derivatives were reported4.

     Synthesis, characterization and biological activity of some new 5-halo-4, 6-
      dimethoxy-2-(alkoxy or aryloxy) pyrimidines were reported5.

     Synthesis and biological evaluation of pyrido(2,3-d)pyrimidine-carboxylate
      derivatives were carried out6.

     A review on emerging anticonvulsants was discussed7.

     Synthesis of some novel 4-(4-chlorophenyl)-6-p-tolyl-+-pyrimidine derivatives and
      their anticonvulsant activity was reported8.

     Antimicrobial studies of 10-substituted-6a, 7-dihydro-6H-7-(4-fluorophenyl)-6-
      phenyl [1]benzopyrano[3,4-c] [1,5]benzothiazepines were reported9.

     Synthesis, spectral studies and antimicrobial activity of 7-chloro-2-alkyl/aryl-4-
      arylidene-3H-1, 5-benzodiazepines were reported10.

     Synthesis, spectral studies and biological activity of 3H-1, 5-benzodiazepine
      derivatives were reported11.

     Synthesis, spectral studies and biological activity of novel 1H-1,4-diazepine
      derivatives were reported12.

     2, 4-disubstituted 1,5-benzodiazepines as potential anti-infectives were studied by
      multiple regression analysis13.

     Novel 1, 4-benzodiazepine derivatives with anti-proliferative properties on tumor
      cell lines were studied14.


                                            4
   6-acetyl-2,4-diamino-7,8-dihydro-9H-pyrimido[4,5-b][1,4]diazepine, an amino
    analogue of a naturally occurring dihydrohomopteridine was synthesized using a
    furazano [3,4-d]pyrimidine precursor15.

   Facile preparation of 9-H-pyrimido [4,5-b][1,4]diazepine derivatives was carried
    out from 4,5-diaminopyrimidines and ethylpyruvate16.

   Bischler –Napieralski cyclocondensation was used in the synthesis of new 11H-
    pyrimido [4, 5-b] [1, 4] benzodiazepines17.

   Novel 8, 9-dihydro-7H-pyrimido [4, 5-b] [1, 4] diazepines as potential antitumor
    agents were synthesized using microwave heating18.

   Synthesis of new indeno[1,2-e]pyrimido[4,5-b][1,4]diazepine-5,11-diones as
    potential anti-tumor agents was carried out19.

   Novel 6,6a,7,8-tetrahydro-5H-naphthol[1,2-e]pyrimido[4,5-b][1,4]diazepines were
    synthesized as potential antitumor agents using microwave irradiation20.

   Chemical aspects of 1, 4 and 1, 5-benzodiazepines were studied21.

   A new class of pyridopyrimidine derivatives: Furo[2,3-d]pyrido[1,2-a]pyrimidines
    were reported22.

   Synthesis and biological testing of Clozapine derived 2,3-dihydro-1H-1,4 and 1,5-
    benzodiazepines with D4 receptor was reported23.

   Anticonvulsant activities of 7-phenyl-5H-thiazolo[5,4-e][1,2,3,4]tetrazolo[5,1-
    c]pyrrolo[1,2-a][1,4]diazepine and 7-phenyl-5H-thiazolo[5,4-e][1,3,4]triazolo[5,1-
    c]pyrrolo[1,2-a][1,4]diazepines was reported24.

   1,5-benzodiazepine derivatives were synthesized using CdCl225.

   synthesis of 2-arylimidazo[1,2-a]pyrimidines and their conversions into 3-bromo-2-
    arylimidazo[1,2-a]pyrimidines using [hydroxy(tosyloxy)iodo]benzene was carried
    out26.

   Synthesis of some novel pyrazolo[3,4-d]pyrimidine derivatives was reported27.

   Conformational analysis of N1, N5-diacetyltetrahydro-1,5-benzodiazepin-2-ones
    using NMR spectra and semiempirical MO calculations was reported28.



                                         5
   3H-1,5-benzodiazepine derivatives were synthesized using heteropolyacids as
    heterogeneous recyclable catalyst29.

   1,5-benzodiazepine derivatives were synthesized using TCT-catalyzed reaction
    under mild condtion30.

   New amino-1,5-benzodiazepines and benzotriazole derivatives were synthesized
    from dimedone31.

   Conformational studies and reactions of 1,4-diazepines and 1,5-diazepines were
    discussed32.

   Synthesis, anticancer activity of some 1-(Bis N, N-(ChloroEthyl)-Amino Acetyl)-
    3,5-Disubstituted 1,2-Pyrazolines were reported33.

   3D QSAR analysis of 2, 4-disubstitued 1, 5-benzodiazepine derivatives as CNS
    depressants was reported34.

   Synthesis and in-vivo anticancer screening of 2-{[Bis-(2-Chloroethyl) Amino]
    Methyl} - 6, 8-Dinitro-1- (4-Substituted Ethyl)-1h-quinazolin-4-One Derivatives
    were reported 35.

   Novel one pot room temperature ionic liquid mediated synthesis of 1,5-
    benzodiazepine ribofuranosides was reported36.

   Various pyrimidine and isoxazole derivatives were synthesized from 1-{4`-[(4``-
    methylpiperazinyl) diazenyl] phenyl}-3-(substituted phenyl) prop-2-en-1-one using
    microwave heating and their antimicrobial activity was reported37.

   Synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines using an efficient
    Heteropolyacid-Catalyzed procedure were reported38.

   In vitro an In Vivo anticancer activity of Bacoside A from Whole plant of Bacopa
    Monnieiri(Linn) were reported39.

   Brief review of cancer was discussed40.




                                         6
6.3 OBJECTIVES OF STUDY

1) To synthesize the proposed derivatives with optimum yield.

2) To purify the synthesized compounds.

3) To characterize the synthesized compounds by Spectral interpretation and by means of
   chemical tests.

4) To evaluate the antimicrobial activity2, 3, 6 and In-vitro antitumor activity33, 35, 39 of the
   synthesized compounds.




                                                 7
7. MATERIAL AND METHODS

7.1 SOURCE OF DATA

1) Chemical abstracts, Medline, websites.
2) Journals and publications.
3) Lab based studies.


7.2 METHODS OF COLLECTION OF DATA:

   1) The chemicals & reagents required for the synthesis and evaluation of the proposed
       compounds will be procured from reputed chemical suppliers like Merck, Ranbaxy,
       Qualigens, Himedia, S.D Fine Chemicals, CDH chemicals, Spectrochem, etc.
  2) SYNTHESIS:
       Conventional methods of synthesis as well as microwave assisted synthesis will be
       attempted. The completion of the reaction will be determined by TLC. Advantages
       and feasibility of the methods will be analyzed.
   3) PURIFICATION AND PHYSICAL CONSTANTS
       The synthesized compounds will be purified by different methods like
       recrystallization,   Fractional-crystallization,   distillation   and   chromatographic
       methods. The purity will be ascertained by TLC and elemental analysis.
               The physical parameters like solubility in various solvents, melting point or
       boiling point, nature of the crystals, colour and percentage yield will be obtained
       after purification by recrystallizing in a suitable solvent.
    4) CHARACTERIZATION
       The synthesized compounds will be characterized by:
       a. Chemical tests for important functional groups.
       b. Elemental analysis
       c. Study of spectral data-IR, NMR and Mass spectroscopy.




                                               8
SCREENING FOR ANTIMICROBIAL ACTIVITY:
A) SCREENING FOR ANTIBACTERIAL ACTIVITY BY DISC DIFFUSION
METHOD: 2, 3, 6.
       Antimicrobial studies will be carried out on both Gram positive and Gram negative
  organisms like Staphylococcus aureus, Bacillus cereus, Escherichia coli, and
  Pseudomonas aeruginosa etc using sterile media like Mueller-Hinton Agar etc by Disc
  Diffusion Method. Zone of inhibition of the synthesized compounds will be noted and
  compared with that of standard drugs like Amoxicillin, Ciprofloxacin etc. The entire
  work will be done using horizontal Laminar Flow hood.


B)     SCREENING FOR ANTIFUNGAL ACTIVITY BY DISC DIFFUSION
             2, 3, 6.
METHOD:
       This will be carried out on organisms like Candida albicans and Aspergillus niger
using media like Sabouraud Dextrose Agar. Zone of inhibition of the synthesized
compounds will be compared with that of standard drugs like Ketoconazole. The entire
work will be done using Horizontal Laminar Flow hood.

SCREENING FOR ANTITUMOR ACTIVITY IN-VITRO METHOD: 33, 35, 39

         Different cell lines like (HT29) colon cancer, (HEPG2) liver cancer, Dalton`s
lymphoma ascites etc will be obtained from different institutes like National center for cell
sciences (NCCS pune) . The cells will be cultured in suitable media like Phosphate buffer
saline solutions or in Dulbecco`s Modified Eagles Medium and will be studied for
cytotoxic activity using different methods like MTT assay.



7.3 DOES   THE   STUDY  REQUIRE ANY   INVESTIGATION OR
    INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER
    HUMANS OR ANIMALS?

                                     -NOT APPLICABLE-



7.4   HAS    ETHICAL       CLEARANCE          HAS     BEEN      OBTAINED        BY    YOUR
INSTITUION IN CASE OF 7.3?
                                     - NOT APPLICABLE-

                                              9
8. LIST OF REFERENCES:
1.   Naik T A, Chikhalia K H. Studies on synthesis of pyrimidine derivatives and their
     pharmacological Evaluation. E-J. Chem 2007 January;4(1): 60-66.

2. Fathalla OA, Zeid IF, Haiba M E, Soliman AM, Abd-Elmoez Sh I, El-Serwy WS.
     Synthesis, antibacterial and anticancer e valuation of some pyrimidine derivatives.
     World journal of Chemistry 2009;4(2): 127-132.

3. Sanjeeva Reddy Ch, Vani Devi M, Rajesh Kumar G, Sanjeeva Rao L, Nagaraj A.
     Synthesis and antimicrobial activity of linked heterocyclics containing pyrazole-
     pyrimidine rings. Indian J. Chem 2011 September;50B: 1181-1186.

4. Mahmoud Refaee Mahoumd, Ahmed Kamel El-Ziaty, Mahmoud Fawzy Ismail,
     Sayed Ahmed Shiba, Synthesis of novel pyrimidine and fused pyrimidine
     derivatives. European Journal of Chemistry 2011;2(3): 347-355.

5. Paniraj AS, Lokanath Rai KM, Prasanna VB, Sanath Kumar Goud P, Vadiraj SG,
     Prosenjit Bose et al. Synthesis, characterization and biological activity of some new
     5-halo-4, 6-dimethoxy-2-(alkoxy or aryloxy) pyrimidines. Der. Pharma. Chemica
     2011;3(3): 63-72.

6. Shanmugasundaram P, Harikrishnan N, Vijey Aanandini M, Satish Kumar M,
     Sateesh J N. Synthesis and biological evaluation of pyrido(2,3-d)pyrimidine-
     carboxylate derivatives. Indian J. Chem 2011 March;50B: 284-289.

7. Nadeem Siddiqui, Jawaid Akhtar Md, Ruhi Ali, Bishmillah Azad, Andalip . An
     updated review: Emerging anticonvulsants. International Journal of
     Pharmaceutical and Biological Archives 2010;1(5): 404-415.

8. Devendra Singh Thakur, Harish Rajak, Peeyush Kumar, Yogesh Vaishnav.
     Synthesis of some novel 4-(4-Chlorophenyl)-6-p-Tolyl+pyrimidine derivatives and
     their anticonvulsant activity. Acta Poloniae Pharmaceutica - Drug Research
     2011;68(6): 993-997.



                                        10
9. Umesh Pant C, Hem Chandra, Shweta Goyal, Priyanka sharma, Seema Pant.
   Synthesis of 1, 5-benzothiazepines: Part XXX-Synthesis and antimicrobial studies
   of 10-substituted-6a, 7-dihydro-6H-7-(4-fluorophenyl)-6-phenyl [1]
   benzopyrano[3,4-c] [1,5] benzothiazepines. Indian J. Chem 2006 March;45B: 752-
   757.

10. Vijai Pathak N, Rahul Joshi, Neetu Gupta. Synthesis, spectral studies and
   antimicrobial activity of 7-chloro-2-alkyl/aryl-4-alkyl/aryl-3-arylidene-3H-1,5-
   benzodiazepines. Indian J. Chem 2007 July;46B: 1191-1197.

11. Rajesh Kumar, Joshi Y C. Synthesis, spectral studies and biological activity of 3H-
   1,5-benzodiazepine derivatives. ARKIVOC 2007;(XIII): 142-149.

12. Rajesh Kumar, Yogesh Joshi C. Synthesis, spectral studies and biological activity
   of novel 1H-1,4-diazepine derivatives. Indian J. Chem 2010 January;49B: 84-88.

13. Bhatia Manish Sudesh, Choudhari Prafulla Balkrishna, Ingale Kundan Bhanudas.
   Multiple linear regression study of 2,4-disubstituted 1,5-benzodiazepine as potential
   anti-infectives. Iranian Journal of Pharmaceutical sciences 2010 Summer;6(3):
   199-208.

14. Jennifer Dourlat, Wang-Qing Liu, Nohad Gresh, Christiane Garbay. Novel 1,4-
   benzodiazepine derivatives with antiproliferative properties on tumor cell lines.
   Bioorg. Med. Chem. Lett 2007;17(9): 2527-30.

15. Peter Boyle H, Enid Hughes M, Hassan Khattab A. Synthesis of a 2,4-
   diaminodihydrohomopteridine, 6-acetyl-2,4-diamino-7,8-dihydro-9H-pyrimido[4,5-
   b][1,4]diazepine, using a furazano[3,4-d]pyrimidine precursor. Tetrahedron
   1991;47(28): 5259-5268.

16. Manuel Melguizo, Adolfo Sanchez, Manuel Nogueras, John Low N, Alan Howie R
   Graciela Andrei et al. Facile preparation of 9-H-pyrimido [4,5-b] [1,4] diazepine
   derivatives from 4,5-diaminopyimidines and ethyl pyruvate . Tetrahedron
   1994;50(47):13511-13522.




                                       11
17. Justo Cobo, Manuel Nogueras, John Low N, Ricaurte Rodriguez. Bischler-
   Napieralski cyclocondensation in the synthesis of new 11H-pyrimido[4,5-
   b][1,4]benzodiazepines. Tetrahedron Lett 2008 December 15;49(51): 7271-7273.

18. Braulio Insuasty, Fabian Orozco, Jairo Quiroga, Rodrigo Abonia, Manuel
   Nogueras, Justo Cobo. Microwave induced synthesis of novel 8,9-dihydro-7H-
   pyrimido[4,5-b][1,4]diazepines as potential antitumor agents. Eur. J. Med. Chem
   2008;43: 1955-1962.

19. Braulio Insuasty, Fabian Orozco, Carolina Lizarazo, Jairo Quiroga, Rodrigo
   Abonia, Mike Hursthouse et al. Synthesis of new indeno[1,2-e]pyrimido[4,5-
   b][1,4]diazepine-5,11-diones as potential antitumor agents. Bioorg. Med. Chem
   2008;16: 8492-8500.

20. Braulio Insuasty, Angelica Gracia, Jairo Quiroga, Rodrigo Abonia, Manuel
   Nogueras, Justo Cobo. Synthesis of novel 6,6a,7,8-tetrahydro-5H-naphthol[1,2-
   e]pyrimido[4,5-b][1,4]diazepines under microwave irradiation as potential anti-
   tumor agents. Eur. J. Med. Chem 2010;45: 2841-2846.

21. Kuch H. Clobazam: Chemical aspects of the 1,4 and 1,5-benzodiazepines. Br. J.
    clin. Pharmac 1979;7: 17S-21S.

22. Gullu M, Utley J H P. A new class of pyridopyrimidine derivatives: Furo[2,3-
   d]pyrido[1,2-a]pyrimidines. Commun. Fac. Sci. Univ. Ank 1999;45B: 93-99.

23. Thomas Hussenether, Harald Hubner, Peter Gmeiner, Reinhard Troschutz.
   Clozapine derived 2,3-dihydro-1H-1,4-and 1,5-benzodiazepines with D4 receptor
   selectivity: synthesis and biological testing. Bioorg. Med. Chem 2004;12: 2625-
   2637.

24. Maryam Shekarchi, Marya Binesh Marvasti, Mohammad Sharifzadeh, Abbas
   Shafiee. Anticonvulsant activities of 7-phenyl-5H-thiazolo[5,4-
   e][1,2,3,4]tetrazolo[5,1-c]pyrrolo[1,2-a][1,4]diazepine and 7-phenyl-5H-
   thiazolo[5,4-e][1,3,4]triazolo[5,1-c]pyrrolo[1,2-a][1,4]diazepines. Iran. J. Pharm.
   Res 2005;1: 33-36.



                                      12
25. Pasha M A, Jayashankara V P. An expeditious synthesis of 1,5-benzodiazepine
   derivatives catalyzed by CdCl2. Indian J. Chem 2006 December;45B: 2716-2719.

26. Ranjana Aggarwal, Garima Sumran. A facile [hydroxy(tosyloxy)iodo]benzene
   mediated synthesis of 2-arylimidazo[1,2-a]pyrimidines and their conversions into 3-
   bromo-2-arylimidazo[1,2-a]pyrimidines. Indian J. Chem 2006 December;45B:
   2690-2695.

27. Ana Oliveira-Campos M F, Abdellatif Salaheldin M, Ligia Rodrigues M. Synthesis
   of some novel pyrazolo[3,4-d]pyrimidine derivatives. ARKIVOC 2007 ;(XVI): 92-
   100.

28. Venkatraj M, Ponnuswamy S, Jeyaraman R. Conformational analysis of N1, N5-
   diacetyltetrahydro-1,5-benzodiazepin-2-ones using NMR spectra and semiempirical
   MO calculations. Indian J. Chem 2008 January;47B: 129-135.

29. Majid Heravi M, Samaheh sadjadi, Hossein Oskooie A, Rahim Hekmatshoar,
   Fatemeh Bamoharram F. An efficient synthesis of 3H-1,5-benzodiazepines
   derivatives catalyzed by heteropolyacids as heterogeneous recyclable catalyst. J.
   Chin. Chem. Soc 2008;55: 842-845.

30. Chun-Wei Kuo, Chun-Chao Wang, Veerababurao Kavala, Ching-Fa Yao.
   Efficient TCT-catalyzed synthesis of 1,5-benzodiazepine derivatives under mild
   conditions. Molecules 2008;13: 2313-2325.

31. Norah Bennamane, Rachedine Kaoua, Lamouri Hammal, Bellara Nedjar-Kolli.
    Synthesis of new amino-1,5-benzodiazepine and benzotriazole derivatives from
    dimedone. Org. Commun 2008;1(3); 62-68.

32. Meanwell NA, Walker MA. 1,4-diazepines. Elsevier Ltd 2008:2-47.

33. Gowramma B, Jubie S, Kalirajan R, Gomathy S, Elango K. Synthesis, anticancer
   activity of some 1-(bis N,N-(chloroethyl)-amino acetyl)-3,5-disubstituted 1,2-
   pyrazolines. International Journal of Pharm Tech Research 2009 April-June;1(2):
   347-352.




                                      13
34. Manish Bhatia S, Prafulla Choudhari B, Kundan Ingale B, Neela Bhatia M, Bandu
   Zarekar E, Deepak Sangale B . 3D QSAR analysis of 2,4-disubstituted 1,5-
   benzodiazepine derivatives as CNS depressants. Digest J. Nanomaterials and
   Biostructures 2009 September;4(3): 579-585.

35. Yuvaraj Govindaraj, Sathyamoorthy, Venkatesh Karthikeyan, Vijyalakshmi
   Melanaphuru, Vivek Agrahari, Sandeep Gupta et al. Synthesis and in-vivo
   anticancer screening of 2-{[bis-(2-chloroethyl) amino] methyl}- 6, 8-dinitro-1- (4-
   substituted ethyl)-1h-quinazolin-4-one derivatives. Academic Journal of Cancer
   research 2009;2(2): 73-77

36. Ashok yadav K, Manoj Kumar, Tripti Yadav, Renuka Jain. A novel one pot room
   temperature ionic liquid mediated synthesis of 1,5-benzodiazepine
   ribofuranosides. Indian J. Chem 2010 April;49B: 461-468.

37. Mistry BD, Desai KR, Rana PB. Conventional and microwave induced Synthesis of
   various pyrimidine and isoxazole derivatives from 1-{4`-[(4``-
   methylpiperazinyl)diazenyl]phenyl}-3-(substitutedphenyl)prop-2-en-1-one and
   studies of their antimicrobial activity. Indian J. Chem 2011 April;50B: 627-633.

38. Rachedine Kaoua, Norah Bennamane, Saliha Bakhta, Sihame Benadji, Cherifa
   Rabia, Bellara Nedjar-Kolli. Synthesis of substituted 1,4-diazepines and 1,5-
   benzodiazepines using an efficient heteropolyacid-catalyzed procedure. Molecules
   2011;16: 92-99.

39. Prakash N S, Sundaram R, Mitra S K. In vitro and In vivo anticancer activity of
   Bacoside A from Whole plant of Bacopa monnieiri(Linn). Am. J. pharmacol.
   Toxicol 2011;6(1): 11-19.

40. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002267/




                                      14
9. SIGNATURE OF THE STUDENT :


10. REMARKS OF THE GUIDE        : Recommended for registration


11. NAME AND DESIGNATION


  11.1) GUIDE               : Prof. C. H. S. VENKATARAMANA
                              Professor and HOD (In-charge)
                                    Department of Pharmaceutical
                                    Chemistry
                                    M.S. Ramaiah College of Pharmacy
                                    Bangalore-560054


  11.2) SIGNATURE               :

  11.3) CO-GUIDE                : Not Applicable

  11.4) SIGNATURE               : Not Applicable


  11.5) HEAD OF THE
          DEPARTMENT            : Prof. C.H.S. VENKATARAMANA
                                  Professor and HOD (In-charge)
                                    Department of Pharmaceutical
                                    Chemistry
                                    M.S. Ramaiah College of Pharmacy
                                    Bangalore-560054



  11.6) SIGNATURE               :

12. 12.1) REMARKS OF THE
          PRINCIPAL             :




  12.2) SIGNATURE               :




                           15

								
To top