Synthesis characterization and pharmacological investigation of by 4w9DQc





1   Name of the candidate and address           NITIN PATEL
    (In block letters)                          S/o Bhanuprasad Patel
                                                At : T.Palla, Post : Madhavas,
                                                (389230)Ta: Lunawada,
                                                Dist : Panchamahal, Gujarat.
2   Name of the institution                     T.M.A.E. Society’s
                                                S.C.S College of Pharmacy
3   Course of Study and Subject                 M.Pharm ( Previous )
                                                Pharmaceutical chemistry.
4   Date of admission to course                 5TH July,2008
5   Title of the topic
                                                 “SYNTHESIS, CHARACTERIZATION, IN-VITRO ANTI-
                                                        OXIDANT AND ANTI-MICROBIAL
                                                       ACTIVITIES OF NOVEL COUMARIN

          Link and coworker found that cattle feeding on spoiled sweet hay suffered from a condition
    characterized by sharp increase of blood clotting time. The pathogenic hemorrhageic principle of
    sweet clover hay was found by them to be 3, 31 - methylenebis – (4-hydroxy Coumarin) popularly
    called Dicoumarol. It was synthesized by reacting 4-hydroxy Coumarin with formaldehyde and
    found to be a good anticoagulant of blood.

        Coumarin is widely available in plant kingdom as the active constituent in various plants.
    Many of natural occurring coumarins posses wide range of biological and pharmacological

         Literature on biological and pharmacological activities of synthetic coumarins is
    innumerous1-4. Coumarins are known to posess anti-inflammatory, antioxidant5, HIV reverse
    transcriptase inhibitory activity6, antiviral7, anti-tumor activity8, cytotoxic agents9,antitubercular10

         The compounds containing thione (>C=S) and thiol (>C-SH) groups occupy an important
    position among organic reagents as they posses many applications in industry, in medicine and
    analytical chemistry. Variety of thiosemicarbazones are synthesized and evaluated for their useful
    biological and pharmacological activities like antiviral11-13, antibacterial and antitubercular
    activity14, antiamoebic acitivity15, anticancer and cytotoxic activities16-17.
          However there are few reports on biological significance of coumarin thiosemicarbazones.
    Hence the present work is designed to synthesize novel thiosemicarbazones of coumarins and to
    evaluate their biological activities like antimicrobial and antioxidant activity.

    6.2 Review of literature:

    An extensive survey of literature to be done by referring chemical abstracts, various international
    research journals in our college library, libraries of Kuvempu university Shimoga, Karnataka
    university Dharwad, Mysore university Mysore and Bangalore university Bangalore, Gulbarga
    University Gulbarga. The literature survey will also be made by visiting the various websites
    through internet and also by availing CD-ROM facilities I.I.S.C Bangalore.

    6.3 Objectives of study:

    The main objective of the present work is to synthesize the novel compounds containing coumarin
    ring and thione group in hope of getting potent biological agents. Biological acivities of
    synthesized compounds like antibacterial and antioxidant activities will evaluated. Antibacterial
    activity of compounds will be evaluated against gram positive and gram negative pathogens by
    MIC method18. Antioxidant potential of the compounds will be carried out by in-vitro models
    against various types of free radicals19-20.


    The necessary data will be generated by laboratory experimentation technique this includes,
       a) Synthesis of target molecules.
       b) Spectroscopic data of new compounds for structural confirmation (I.R.,H1 NMR and Mass
           spectra etc).
       c) Anti-microbial and In vitro Anti-Oxidant screening and result of activities.

    7.1 Source of data:

                  Various national and international journals.
                  Chemical abstracts.
                  Standard text books for carrying out screening of pharmacological activities.
                  Indian pharmacopoeia.
7.2 Methods of collect of data:

       (Including sampling procedure if any)

  a) Synthetic methodology

         Synthetic strategy for target molecules involves followings procedure.

       The reaction of salicylaldehyde with Ethylacetoacetate in presence of piperidine give
  yellow solid mass of Acetyl-Coumarin21-23, which was fused with substituted
  thiosemicarbazide in ethanol medium in presence of glacial acetic acid to afford the
  corresponding Acetyl Coumarin thiosemicabazone derivatives.
        Reaction will be monitored by TLC and product purified by recrystllisation.

      b) Spectroscopic data:

     IR of all new compounds will be obtained by using spectrophotometers available in our
  college, NMR and mass spectroscopic data will obtain from I.I.Sc Bangalore and I.I.T. Madras

      c) In vitro Anti-Oxidant and Biological screening:

           Anti-Microbial activity 18: All the synthesized compounds will be evaluated for
      Anti-microbial activity by MIC method.

            In-Vitro Anti-Oxidant activity 19-20: Selected compounds will be subjected to screening
      for In-vitro Anti-Oxidant activity.

7.3     Does the study require any investigation (or) interventions to be conducted on
        patients (or) other humans (or) animals? If so please describe briefly:

        1) Borges F, Roleira F, et al. “Simple coumarin and analogues in medicinal chemistry
           occurrence, synthesis and biological activity”. Curr Med Chem.2005; 12(8):887-916.

        2) Curini M, Cravotto G, et al. “Chemistry and biological activity of natural and
           synthetic prenyloxycoumarins.” Curr Med Chem.2006; 13(2):199-222.

        3) Kulkarni MV, et al. “Recant advance in coumarins and 1-azacoumarins as versatile
           biodynamic agent.” Curr Med chem. 2006; 13(23):2795-818.

        4) Hoult JR, Paya M. “Pharmacological and biochemical action of simple coumarins:
           natural product with therapeutic potential.” Gen pharmacology. 1996; 27(4):713-722.

        5) Litina dj, et al. “Natural and synthesis coumarin derivative with anti-inflammatory
           /antioxidant activities.” Curr Pharm. Des. 2004; 10(30):3813-3833.

        6) Kostova I. “coumarins as inhibitor of HIV reverse transcriptase.” Curr HIV Res.
           2006; 4(3):347-63.

        7) Barnard Dale L .et al. “Coumarins and pyranocoumarines, pontential novel
           pharmacophores for inhibition of measles virus replication.” 2002; 13:1:39-59.

        8) Weber us, et al. “Antitumor activities of coumarin, 7-hydroxy coumarin and its
           glucuronide in several human tumor cell lines.” Res. Commun Mol pathol
           pharmacology. 1998; 99(2):193-206.

        9) Kostova I. “Synthetic and natural coumarins as cytotoxic agent.” Curr Med Chem.
           Anticancer agent. 2005; 5(1):29-46.

        10) Manvar et al. “Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin -
            4-acetic acid benzlidene hydrezide.” Eur J Med chem. 2008; 43(11):2395-403.

        11) Nancy E. lem, et al. “Antiviral activity of N-Etylisatin B-thosemicarbazone in
           vaccinia infected mice.” The journal of immunology, 1965; 94:794-804.

        12) Bauer, D.J. et al. “The structure activity relationships of antiviral chemotherapeutic
            activity of isatin ?- thiosemicabazones.” Datos del recurso.

        13) Surendra P. singh, et al. “Synthesis of some new substituted thiosemicarbazides as
            potential antiviral agent.’’ Journals of Archiv der Pharmazia 2006; 316(10):817-821.

        14) Koti rajesh, S. et al. “Synthesis and evaluation of the antibacterial and antitubercular
            activity of some N1-aral-N4–(3-chloro-4-fluorophenyl)thiosemicabazones and copper
            Complexes.” Arzneimittel-forschung 2005; (2):107-113.
15) Agarwal, et al. “ Synthesis and anti amoebic activity of metronidazole
    thiosemicarbazones analogues.” European Journal of medical chemistry.” 2008;

16) Weizhou, xi- Wen et al. “Synthesis and anticancer activity of thosemicarbazone.”
    Bioorganic & medicinal chemistry letters.” 2006; 16(8):2213-2218.

17) Ahmed M.M., El-saghier et all. “Synthesis and antibacterial activity of some new
   fused chromenes. ” ARKIVOC. 2007; 16: 83-91.

18) Banjamin Prescott. “4-Hydroxy 2-butenone thiosemicarbazones a pontecial
    anticancer agent.” Journal of medicinal chemistry.1967; 10(3):484-485.

19) M.S.More, et al. “Synthesis, characterization, antioxidant and antimicrobial activity
    of different heterocycle derived from 3-formyl chrimones.” Oriental journal of
    chemistry 2007; 23:329-334.

20) R.Suthakaran, M.Bhagavan.,S.Kavimani1, et al. “Synthesis, Antioxidant, Anti-
    microbial activity of [2-(5-substituted aryl 1- N-substituted aryl amino methyl)
    pyrazol-3-yl] benzofuran.” Rasayan Journal of chemistry. 2008 1:1:39-45.

21) Y. Rajendra Prasad .,P.Ravikumar., “Synthesis and antimicrobial activity of some
    novel chalcones of 2-hydroxy -1-Acetonapthone and 3-acetyl coumarin.” Journal of
    chemistry 2006; 3:13:236-241.

22) Vijayananda Krishna Revankar., Ph.D. Thesis on “Chemistry of some Coordination
    Compounds”. Submitted to Karnatka university Dharwad., 1988; 114-115 .

23) A.I.Vogel, “A Text Book of Practical Organic Chemistry”., ELBS, 4TH Edition ,
9    Signature of Candidate
                                                   (MR.NITIN PATEL)
                                        The mentioned title compound will be
10   Remarks of the guide               synthesized and screened for the activity.
                                        They are confirmed by the Spectroscopical
                                        Studies under the guidance of me in the
                                        P.G. Department of Pharmaceutical
                                        Chemistry of our College.

11   Name and Designation               Dr. B.H.M. JAYAKUMAR SWAMY
     (in block letters)                 Professor,
                                        P.G. Dept. of Pharmaceutical
     11.1 GUIDE                         Chemistry,
     Guide ship reference no. of        S.C.S College of Pharmacy,
     RGUHS                              Harapanahalli-583131.
     ACA/CDC/PGT-M.Ph/SCS/02/2005-06     Davanagere-Dist.
     Date: 27-09-2005.

     11.2 Signature.

     11.3 Co-guide(if any)
     Guide ship reference no. of        Dr. B.SHIVAKUMAR
     RGUHS                              Professor,
     ACA/PGT-M.Ph/scs/02/99-2000/5821   P.G. Dept. of Pharmaceutical
     Date:05-06-1999                    Chemistry,
                                        S.C.S College of Pharmacy,

     11.4 Signature

                                        Dr. E. JAYACHANDRAN
     11.5 Head Of The Department        Professor and Head.
     Guide ship reference no. of        P.G. Dept. of Pharmaceutical
     RGUHS                              Chemistry,
     ACA-2/RP-TEA/01/97-98              S.C.S College of Pharmacy,
     Date:.03-06-1998.                  Harapanahalli-583131.

     11.6 Signature
12   12.1 Remarks of the Principal

     12.2 Signature
                                              (Dr. S. RAMACHANDRA.SETTY)

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