Structural and Biological Activity Studies on Metal Complexes Containing Thiosemicarbzone and Isatin  Based Schiff Base: A Review

 

Md. Saddam Hossain, C. M. Zakaria, Md. Kudrat-E-Zahan*

Department of Chemistry, University of Rajshahi, Rajshahi-6205, Bangladesh.

*Corresponding Author E-mail: kudrat.chem@ru.ac.bd

Thiosemicarbazones are Schiff base ligands which have achieved much attention by the scientist over the decades as potential drug agent. Isatin is an endogenous compound isolated in 1988 and reported to possess a wide range of structural and biological activities involving the central nervous system. The versatility  and flexibility of  Schiff base compounds having, acyl, aroyl and heteroacroyl  ligands have additional  donor  sites >C=O, >C=N-,  >C=S etc. have made the Schiff bases to act  as good complexing  agents that  form a variety of complexes with various transition and inner transition metals which also emphasized the attention of many researchers. Azomethine linkage(-CH=N-) of Schiff base play an significant role in medical field with so many pharmacological applications such as antimicrobial, antiviral, anti-tubercularculosis, anti-HIV, anti-diuretic and anticancer activity. The potency of these pharmaceutically useful drugs in treatment of microbial infections and other activities inspired the scientist for the development of some more potent and significant compounds and metal complexes over the years. Schiff base ligands are considered privileged ligands because they are easily prepared by a simple condensation reaction of an aldehyde and primary amines. In this review, the synthesis, biological activities along with application of Schiff base derived from isatin and thiosemicarbazides and their metal complexes are summarized.

 

 

 

1. INTRODUCTION:

Schiff bases are condensation products of primary amines with carbonyl compounds and they were first reported by Hugo Schiff in 1864. The common structural feature of these compounds is the azomethine group with a general formula RHC=N-R^/ where R and R^/ are alkyl, aryl, cyclo alkyl or heterocyclic groups which may be variously substituted. These compounds are also known as anils, imines or azomethines¹.

 

Metals have played an significant role in biological systems over the years. Many are important to our diets in varying quantities, although people have only recently realized their significance. Introducing metal ions into a biological system may be carried out for therapeutic or diagnostic purposes, although these purposes overlap in many cases. Metals not only provide path for synthesis, but they also introduce functionalities that enhance drugs action. The chemistry of the transition metal complexes of thiosemicarbazones became largely appealing because of their broad profile of pharmacological activity that provides a diverse variety of compounds with different activities^2–5. Bis-Schiff base ligands and their coordination compounds having  multifunctional groups play an important role in the areas of stereochemistry, structure of science, spectroscopy, magnetic fields⁶. In recent years, sulfur containing ligands such as dithiocarbamates and thiosemicarbazones and their transition metal complexes have received more attention in the area of medicinal chemistry, due to their pharmacological properties, such as antiviral, antibacterial, antifungal, antiparasitic, and antitumor activities^7-12. Isatin Schiff and Mannich bases were reported to demonstrate a wide range of biological activities such as antibacterial, antifungal, antiviral , anti-HIV, antiprotozoal, and antihelminthic activities^13–21. Schiff base of S-methyldithiocarbazate with isatin has been reported to behave as a versatile chelating agent exhibiting variable denticity towards metal ions²².

 

2. PREPARATION OF SCHIFF BASE:

There are several reaction pathways to synthesise Schiff bases. The most common is an acid catalysed condensation reaction of amine with an aldehyde or ketone under refluxing conditions (Scheme -1). The first step in this reaction is an attack of nucleophilic nitrogen atom of amine on the carbonyl carbon, resulting in a normally unstable carbinolamine intermediate. Due to the elimination of one molecule of water a C=N bond is formed and the product is called imine. Many factors affect the condensation reaction, for example the pH of the solution as well as the steric and electronic effects of the carbonyl compound and amine. In acidic solutions the amine is protonated, thus cannot function as a nucleophile and the reaction cannot proceed. Furthermore, in very basic reaction conditions the reaction is hindered as sufficiently protons are not available to catalyse the elimination of the carbinolamine hydroxyl group. In general, aldehydes react faster than ketones in Schiff base condensation reactions as the reaction centre of aldehyde is sterically less hindered than that of ketone. Furthermore, the extra carbon of ketone donates electron density and thus makes the ketone less electrophilic compared to aldehyde. For preparation of the bridged Schiff’s bases a diamine compound is required with two molecules of aldehyde or ketone according to the structure of the product of interest as in the following reaction.

 

Scheme-1: Preparation of Schiff base

 

Some synthesis procedure of Schiff base ligand derived from Isatin and Thiosemicarbazide are shown below;

Md. Kudrat-E-Zahan  and et al were synthesized a novel bis imine Schiff base ligand derived from isatin and diethylene triamine, “Synthesis, Characterization and Antimicrobial Activity of Cd(II), Ni(II), Co(II) and Zr(IV) Metal Complexes of Schiff Base Ligand Derived from Diethylenetriamine and Isatin” (Asian J. Research Chem. 7(7): July 2014).

 

Scheme 2:Synthesis of Bis(indoline-2-one)diethylenetriamine

 

M. P. Sathisha and et al was prepared Bis-Isatin thiocarbohydrazone Schiff base ligand., “Synthesis, Structure, Electrochemistry, and Spectral Characterization of Bis-Isatin Thiocarbohydrazone Metal Complexes and Their Antitumor Activity Against Ehrlich Ascites Carcinoma in Swiss Albino Mice” Hindawi Publishing Corporation Metal-Based Drugs Volume 2008, Article ID 362105, 11 pages

 

Scheme-3: Preparation of Schiff base ligand

S. S. Shivakumar and et al were synthesized Schiff base ligand from thiosemicarbazide Hindawi Publishing Corporation International Journal of Corrosion Volume 2013, Article ID 543204, 13 pages

 

Scheme-4: Preparation of Schiff base ligand

 

Zeng-Xin Liu et al prepared Schiff base ligand by treating 4-Methyl-3-thiosemicarbazide with appropriate aldehydes,  J. Chil. Chem. Soc., 60, Nº 2 (2015).

 

Scheme-5: Preparation of Schiff base ligand

 

Xinde Zhu and et al prepared Schiff base ligand derived from 3,4-dihydroxy Benzaldehyde and thiosemicarbazide, “Synthesis, characterization and biological activity of the Schi base derived from 3,4-dihydroxybenzaldehyde and thiosemicarbazide, and its complexes with nickel(II) and iron(II)” Transition Met. Chem., 22, 9-13 (1997)

 

Scheme-6:Synthesis of Schiff base ligand

 

Ahlam J et al  were synthesized Schiff base ligand derived from isatin and dithiooxamide,“ Synthesis and Characterization of New Schiff Bases Derived from N (1)-Substituted Isatin with Dithiooxamide and Their Co(II), Ni(II), Cu(II), Pd(II), and Pt(IV) Complexes” Hindawi Publishing Corporation Bioinorganic Chemistry and Applications Volume 2009, Article ID 413175, 12 pages

 

Scheme-7:Synthesis of Schiff base ligand

 

Ayman El-Faham and et al were synthesized a series of Isatin derivatives, “Microwave Synthesis, Characterization  and Antimicrobial Activity of Some Novel Isatin Derivatives” Hindawi Publishing Corporation Journal of Chemistry Volume 2015, Article ID 716987, 8 pages. A mixture of isatin (5mmol) and potassium carbonate (8mmol) in DMF (10 mL) was stirred for 10minutes at room temperature. Alkyl halides (6mmol; benzyl bromide for preparation of 1c, 1d, and 1e; CH₃I for preparation of 1b; and1,3-dibromoethane for preparation of 1f) were added dropwise to the reaction mixture and then the reaction was microwave irradiated using a multimode reactor (Synthos 3000, Anton Paar GmbH, Graz, Austria) (1,400W maximum magnetron). The vessels were heated for 5 minutes at 80°C and held at the same temperature for a further 5 minutes (400 W). Cooling was accomplished by a fan (5 minutes). The final product was dried and recrystallized from ethanol.

 

Scheme-8: Synthesis of Schiff base ligand

 

Tarek Aboul-Fad and et al were synthesized Schiff base ligand derived from isatin and isonicotinic acid hydrazide, “Synthesis, Antitubercular Activity and Pharmacokinetic Studies of Some Schiff Bases Derived from 1- Alkylisatin and Isonicotinic Acid Hydrazide (INH)” Arch Pharm Res Vol 26, No 10, 778-784, 2003

 

 

Scheme-9: Synthesis of Schiff base ligand

 

Elena Pahontu and coworker was synthesized thiosemicarbazone derivative and shown Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones. Willey, J. Cell. Mol. Med. Vol 19, No 4, 2015 pp. 865-878.

 

 

Scheme-10: Synthesis of Schiff base ligand

 

3. Bioactivity of Metal Thiosemicarbazone:

3.1 Antimicrobial Activity:

One of the most promising areas in which thiosemicarbazone compounds are being developed is their use against microorganism.  K. G. O. Casas and coworkers have synthesized the Cu(II) complex with schiff bases derived from aryl-S-benzyildithiocarbazate²³ and was shown good antibacterial activity. M. Emayavaramban and et al were synthesized some novel 5-bromo fluoro benzaldehydeoxime and semicarbazone under ultrasonic irradiation and shown antibacterial activity²⁴.  Salman A. Khan and et al were prepared some  Novel Thiosemicarbazone and Its Cu(II), Ni(II), and Co(II) Complexes and determine its  in vitro antibacterial activity²⁵. Fakruddin and co worker synthesized Schiff base metal complexes of Cr(III), Co(II), Ni(II) and Cu(II) derived from 2, 6-pyridine dicarboxaldehyde-Thiosemicarbazone (PDCTC) by conventional as well as microwave methods. In conventional method the metal complexes was prepared by the mixing of equal moles of metal salts dissolved in the methanol followed by addition of NaOAc (metal: ligand) in 1:1ratio. The precipitated complex was, filtered washed with ether and recrystallized with ethanol and dried under the reduced pressure over anhydrous CaCl₂ in a desiccator while in microwave method the ligand and the metal salts was mixed in 1:1 (metal: ligand) ratio in a grinder. The Schiff base and metal complexes displayed good activity against the Gram-positive bacteria Staphylococcus aureus, the Gram-negative bacteria Escherichia coli and the fungi Aspergillus niger and Candida albicans. The antimicrobial results also indicated that the metal complexes displayed better antimicrobial activity as compared to the Schiff bases ligand. Chelation tends to make the ligand act as more powerful (Fig. 1) and potent bactericidal agent²⁶. Gajendra Kumari and co workers²⁷ synthesized and characterized M(III) complexes of Cr, Mn and Fe with a Schiff base derived from 2-amino-4-ethyl-5-hydroxybenzaldehyde and thiocarbohydrazide by several techniques. The Schiff base ligand and the complexes were also tested for their antimicrobial activity (against the bacteria Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus megaterium, and the fungi Kluyveromyces fragilis, Rhodotorula rubra, Candida albicans and Trichoderma reesei) to assess their inhibiting potential. S. M. S. Shariar co workers²⁸ synthesized Schiff base Benzophenone Thiosemicarbazone derived from thiosemicarbazide and Benzophenone and the compound was used to study their antibacterial activities against some pathogenic bacteria by disc diffusion method. Benzophenone thiosemicarbazone showed significant antibacterial activity as compared with that of Kanamycin. The compounds was found to possess cytotoxic effect. Minimum inhibitory concentration of this compound was also determined. The antibacterial activities of this compound were measured in terms of zone of inhibition. The test compounds showed a good sensitivity against a number of pathogenic bacteria. D. Nasrin and co workers²⁹ in view of the antimicrobial activity of a series of nickel, copper and zinc complexes of tridentate Schiff base derived from the condensation reaction of S-benzyl dithiocarbazate with 2- hydroxyl acetophenone have been synthesized and found to be potential antimicrobial agents. An attempt is also made to correlate the biological activities with geometry of the complexes. The synthesized compounds have been evaluated for their antibacterial and antifungal studies. The in-vitro biological screening effects of the investigated compounds were tested against the bacterial species Shigella dysenteriae, Salmonella typhi and Bacillus cereus and fungal species Fusarium equiseti, Macrophomina phaseolina, Botrydiplodia theobromae and Alternaria alternate. Elena Pahontu and et al were synthesized Cu(II), V(V) and Ni(II) complexes with Schiff base ligand derived from 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone and 4-ethyl-thiosemicarbazide and shown Antibacterial, antifungal and in vitro antileukaemia activity³⁰. Pandeya and coworkers Schiff and Mannich bases derived from isatin derivatives and N-[4-(4'-chlorophenyl)thiazol-2- yl]thiosemicarbazide and was shown antibacterial antifungal and anti-HIV activity³¹. Yidliz. M, Dulger and et al were synthesized Schiff base metal complexes derived from thiosemicarbazide with some 2-hydroxyaldehydes and shown their antibacterial property³².  Prasad. S, Agarwal and his coworkers Cobalt (II) complexes of various thiosemicarbazones of 4-aminoantipyrine and shown its antibacterial property³³. A K Parekh and K.K Desai were synthesized some  thiosemicarbazone Schiff base ligand and shown their antibacterial activity³⁴. N. Murthy and his coworkers were prepared copper (II) complexes with phenylglyoxal bis-(thiosemicarbazones) and determine its antibacterial activity³⁵. M.B. Ferrari and et al were synthesized Ni(II) complexes of P-fluorobenzaldehyde thiosemicarbazones and shown their biological activity³⁶. B. L, Latheef and coworkers were synthesized copper (II) complexes of thiosemicarbazones derived from salicylaldehyde and containing ring incorporated at N (4)- position and shown its antimicrobial activity³⁷. Kalapala Venkatesh and et al were prepared some new thiosemicarbazide derivatives and their transition metal complexes³⁷. Urbain C. Kasséhin and his coworkers were  shown Trypanocidal activity of a thioacyl-thiosemicarbazide derivative associating both immunostimulating thalidomide and anti-parasitic thiosemicarbazide pharmacophores³⁸. K. Alomar and et al were synthesized cobalt(II), nickel(II) and copper(II) complexes with 3-thiophene aldehyde thiosemicarbazone and investigated their biological activity³⁹. M. R. Maurya and et al were synthesized Dioxovanadium(V) and 𝜇-oxo bis[oxovanadium(V)] complexes containing thiosemicarbazone based ONS donor set and investigate their antimicrobial activity⁴⁰. S. Padhye and et al copper(II) complexes of 4-alkyl/aryl-1,2-naphthoquinones thiosemicarbazones derivatives and determined as potent DNA cleaving agent⁴¹. R. P. Gupta and et al were synthesized some Mannich bases of 1-cyclohexylidene-N(1,2-dihydro-2-oxo-3H-indol-3-ylidene) thiosemicarbazones and determined their antibacterial activity [42]. T. A. Yousef and et al were synthesized Co(II), Cu(II), Cd(II), Fe(III) and U(VI) complexes containing a NSNO donor ligand and investigated there in vitro antibacterial and DNA cleaving property [43]. Moamen S. Refat and et al were synthesized Mn(II), Fe(III), Cr(III) and Zn(II) complexes derived from the ligand resulted by the reaction between 4-Acetyl Pyridine and Thiosemicarbazide and determine their antibacterial property⁴⁴. Xinde Zhu and et al were prepared nickel(II) and iron(II) complexes with Schiff base derived from 3,4-dihydroxybenzaldehyde and thiosemicarbazide⁴⁵. Moamen S. Refat and his coworkers were synthesized new Copper(II) and Manganese(II) Complexes with 1,2,4-Triazines Thiosemicarbazide and determined their biological activity⁴⁶. Wilfredo Hernández and his coworkers were synthesized New Palladium(II) Thiosemicarbazone Complexes and shown their cytotoxic activity against human tumor cell⁴⁷. G. Pelosi and et al were shown Antiretroviral activity of thiosemicarbazone metal complexes⁴⁸. A. Karak uc and et al were synthesized Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2- carboxaldehydes and shown their antiviral and cytotoxic activities⁴⁹. P. Genova and et al were synthesized palladium(II) complexes with bis(thiosemicarbazone) and shown toxic effect on herpes simplex virus growth⁵⁰. I. Kizilcikh and et al were synthesized a series of thiosemicarbazones and their Zn(II) and Pd(II)complexes and investigated their antibacterial activity⁵¹. T. Rosu and were synthesized transition metal complexes with thiosemicarbazones and determined their antibacterial activity⁵². M. Er, Y. Unver  and et al were prepared some new tetra-thiosemicarbazones and their cyclization reactions and shown their biological activity⁵³. S. Chandra and M. Tyagi were synthesized Ni(II), Pd(II) and Pt(II) complexes with ligand containing thiosemicarbazone and semicarbazone moiety and investigate their antiviral activity⁵⁴. S. S. Konstantinovi´c and et al were synthesized some isatin-3-thiosemicarbazone complexes and determined their antimicrobial activity⁵⁵. R. V. Singh and et al were synthesized  palladium(II) and platinum(II) complexes of thiosemicarbazone Schiff base ligand⁵⁶.

 

 

3.2 Ribonucleotide Reductage:

The first breakthrough in the comprehension of the antitumor effect of thiosemicarbazones were obtained in the Sixties and deserves a brief résumé. The anti-leukemic effect of  2-formylpyridine thiosemicarbazone was first reported by Brockman et al.⁵⁷ in 1956. Almost ten years later, in 1965, French et al.⁵⁸ formulated hypotheses about the mode of action of the α(N)-heterocyclic thiosemicarbazones Ribonucleotide reductase is an iron-dependent enzyme that promotes the reduction of ribose to deoxyribose through a free radical mechanism that is triggered by a tyrosyl radical. Inhibition of this enzyme leads to a block in the synthesis phase of the cell cycle and eventually to cell death by apoptosis.They also indirectly demonstrated that the active species was the iron(II) complex of 1 formylisoquinoline thiosemicarbazone. In fact, it was later discovered that iron and copper complexes are by far more active than the free ligands⁵⁹. A reasonable mechanism was proposed by Thelander et al.⁶⁰ who proved, by exposing ribonucleotide reductase to the aforementioned molecules, that it is the tyrosyl free radical of the enzyme that is targeted by the drug and that the thiosemicarbazone complex inhibits the enzyme by destroying the radical. This mechanism requires oxygen and excludes the role of thiosemicarbazones as simple iron chelators. They also report that the reaction is reversible, and this is in agreement with the experimental observations. The fact that 1-formylisoquinoline thiosemicarbazone inhibits more strongly ribonucleotide reductase than 2- formylpyridine thiosemicarbazone gave an indirect hint about the fact that in the enzyme there must be a hydrophobic pocket or patch with which the aromatic system interacts, which could justify the fact that methylation on the aromatic ring of 2-formylpyridine thiosemicarbazone renders this compound more active. In search of an optimum bulk for the aromatic fragment Agrawal et al.⁶¹ identified it with 2- formyl-4-(3-amino)phenylpyridine thiosemicarbazone that was the most active of the 3-aminophenyl derivatives. The most active compound found in the isoquinoline series was instead 1-formyl-5-aminoisoquinoline thiosemicarbazone⁶². Two recent interesting papers by Kowol et al.^63,64 report the synthesis, characterization and biological assays of complexes of Fe(III) and Ga(III) (this latter is an ion known for inhibiting  ribonucleotide  reductase and for its antiproliferative properties). L. Otero and et al were synthesized Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes and investigated DNA and redox metabolism as potential therapeutic targets⁶⁵. P. Chellan, T. Stringer, A. Shokar et al were synthesized in vitro evaluation of palladium(II) salicylaldiminato thiosemicarbazone complexes against Trichomonas vaginalis⁶⁶. N. A. Lewis and et al were synthesized vanadium(IV) complexes with a Schiff base and thiosemicarbazones as mixed ligands and shown its antitumor activity⁶⁷. E. Ramachandran and his coworkers were synthesized Ni(II) and Pd(II) thiosemicarbazone complexes and determined DNA binding, antioxidant and cytotoxicity activity⁶⁸. U. Kulandaivelu, V. G. Padmini, K. Suneetha et al were synthesis novel thiosemicarbazide derivatives and shown their antibacterial and anticancer property⁶⁹. B. Atasever, B. Ulk useven and et al were determined Cytotoxic activities of new iron(III) and nickel(II) chelates of some S-methyl thiosemicarbazones on K562 and ECV304 cells⁷⁰. M. X. Li, C. L. Chen, D. Zhang  and et al were synthesized Mn(II), Co(II) and Zn(II) complexes with heterocyclic substituted thiosemicarbazones and determines their antitumor activity⁷¹. V. Vrdoljak, I. Dilovi´c, M. Rubˇci´c et al were synthesized thiosemicarbazonato molybdenum(VI) complexes and investigated  there in vitro antitumor activity⁷².

 

4. Biological Activity of Isatin Schiff base Metal Complexes:

M. P. Sathisha, V. K. Revankar, and K. S. R. Pai were synthesized Bis-Isatin Thiocarbohydrazone metal complexes and shown their antitumor activity against Ehrlich Ascites carcinoma in Swiss Albino Mice⁷³. Garima Vatsa, O. P. Pandey and S. K. Sengupta were synthesized Titanocene Chelates of Isatin-3- Thiosemicarbazones and shown their toxicity property⁷⁴. Ahmed M. Naglah, Hassan M. Awad  and et al were synthesized novel isatin Schiff bases linked to nicotinic acid via certain amino acid bridge and described their antibacterial activity⁷⁵. S. N. Pandeya, S. Smitha and et al were prepared some isatin derivatives and shown their biological activities⁷⁶. W. Chu, J. Zhang, C. Zeng et al were synthesized N-benzylisatin sulfonamide analogues and shown as potent caspase-3 inhibitors⁷⁷. W. Chu, J. Rothfuss, Y. Chu and et al were synthesized and determined in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6⁷⁸. Z. H. Chohan, H. Pervez and et al were prepared isatin based transition metal complexes and shown their antibacterial and antifungal property⁷⁹. B. R. Nathani, K. S. Pandya and et al were synthesized some isatin derivatives and shown their antimicrobial activity⁸⁰. T. Aboul-Fadl, H. A. Abdel-Aziz and et al were  shown Schiff bases of indoline-2,3-dione as  potential novel inhibitors of mycobacterium tuberculosis (Mtb) DNA gyrase⁸¹. Ahlam J. Abdul-Ghani and Asmaa M. N. Khaleel were synthesized new Schiff base ligand derived from  N (1)-Substituted Isatin with Dithiooxamide and their Co(II), Ni(II), Cu(II), Pd(II), and Pt(IV) Complexes⁸². G. Cerhiaro and A. M. D. Ferreira were synthesized Oxindoles and copper complexes with oxindole-derivatives as potential pharmacological agents⁸³. V. K. Sharma, S. Srivastava, and A. Srivastava were  synthesized novel coordination complexes of the trivalent ruthenium, rhodium and iridium with hydrazones derived from isatin hydrazide and various aldehydes and investigate their biological activity⁸⁴. R. M. Abdel Rahman and et al were synthesized  of some new 3-substituted 1,2,4-triazino-indole derivatives and related compounds and determine them as  potential antifungal agent⁸⁵. S. N. Pandeya, A. S. Raja, and J. P. Stables were synthesized isatin semicarbazones as novel anticonvulsants-role of hydrogen bonding⁸⁶. T. R. Bal, B. Anand, P. Yogeeswari, and D. Sriram were prepared isatin β-thiosemicarbazone derivatives and evaluated as anti HIV active agent⁸⁷. N. M. A. Al-Abidy was synthesized new Mannich- Schiff bases and some metal complexes derived from isatin, 3-amino-1,2,4-triazol and dithiooxamide⁸⁸. Ahlam J. Abdulghani and Nada M. Abbas were synthesized some new Schiff and Mannich bases and some metal complexes derived from isatin and dithiooxamide and evaluated their biological activity⁸⁹. S. N. Pandeya, D. Sriram, G. Nath, and E. De Clercq were synthesized some Schiff and mannich bases of isatin and its derivatives antimpyrimidine also evaluated their antimicrobial activity⁹⁰. D. Maysinger and et a l were synthesized some isatin analogue and determine their antimicrobial activity⁹¹. Ayman El-Faham and et al were synthesized some novel isatin derivatives and shown their biological activity⁹². M. C. Pirrung, S. V. Pansare and et al were shown isatin-𝛽-thiosemicarbazones as anti-poxvirus agents⁹³. A. Jarrahpour, D. Khalili were synthesized some new bis-Schiff bases of isatin and their derivatives and evaluated their antimicrobial, antifungal and antiviral activity⁹⁴. M. Verma, S. N. Pandeya and et al were shown the anticonvulsant activity of isatin derivatives⁹⁵. Sonika Jain, Anamika Sharma were synthesized Some Novel Trisubstituted s-Triazine Derivatives Based on Isatinimino, Sulphonamido, and Azacarbazole and evaluated their antimicrobial activity⁹⁶. G. S. Singh, T. Singh and et al were synthesized new isatin-based spiroazetidinones and investigate their anticonvulsant activity⁹⁷. Ronald Sluyter and Kara L. Vine and et al  were shown N-Alkyl-Substituted Isatins Enhance P2X7 Receptor-Induced Interleukin-1𝛽 Release from Murine Macrophages⁹⁸. Ravi Jarapula and  Kiran Gangarapu were prepared some isatin derivatives and shown their in vitro antiviral activity and molecular docking study⁹⁹. K. Han, Y. Zhou, F. Liu et al  were design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl) isatin derivatives as anticancer agents¹⁰⁰. Mohd Abdul Fatah Abdul Manan and et al were shown crystal structure and cytotoxicity of centrosymmetric copper(II) complex derived from S-methyldithiocarbazate with isatin¹⁰¹. Patitungkho S, Adsule S, Dandawate P and et al were shown anticancer property of Cu(II) complexes of isatin¹⁰². Mohd Abdul Fatah Abdul Manan and et al were synthesized  S-Benzyldithiocarbazate Schiff Bases Derived from 5-Fluoroisatin, 5-Chloroisatin, 5-Bromoisatin and evaluated their crystal structure and cytotoxicity effect¹⁰³. Natarajan Raman , Sivasangu Sobha, Liviu Mitu and et al were synthesized isatin-derived tyramine bidentate Schiff base and its metal complexes also evaluated their structural elucidation, DNA interaction, Biological property and molecular docking model¹⁰⁴ as shown in fig-1(a), 1(b), 1(c), 1(d) and 1(e).

 

Fig. 1(a): Interaction of the complexes [CuL2Cl2] and [ZnL2Cl2] with d(CGCGAATTCGCG) strands of DNA by the minor groove binding approach

 

Fig. 1(b): Crystal structure of Staphylococcus aureus  sortase-A (PDB ID1T2P)

 

Fig. 1(c): The binding model of the Schiff base complex [ZnL₂ CL₂] in the enzyme active site of Staphylococcus aureus sortase-A

 

Fig. 1(d): The binding model of the Schiff base complex [CuL2Cl2] in the enzyme active site of Staphylococcus aureus

 

Fig. 1(e): The binding model of the Schiff base complex [NiL2Cl2] in the enzyme active site of Staphylococcus aureus sortase-A

 

C. Agatha Christiea, C. Shijub and T. F. Abbs Fen Rejia were synthesized Co(II), Ni(II), Cu(II) and Zn(II) complexes derived from isatin monohydrazone and furfuraldehyde also investigated their biological ^activity105. Nu´bia Boechat, \Warner B. Kover and et al were synthesized new 3-hydroxy-2-oxo-3 trifluoromethylindole  and evaluated  as potential HIV-1 reverse transcriptase inhibitors¹⁰⁶. Gurunath S. Kurdekar, M. P. Sathisha and et al were synthesized Metal complexes of Co(II), Ni(II), Cu(II), and Zn(II) with ligands derived from 4-aminoantipyrine, 2-hydroxy-3-formylquinoline, and isatin as potent anticonvulsant agents¹⁰⁷. K. Rama Krishna Reddy and K. N. Mahendra were synthesized Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II), dioxouranium(VI), and Th (IV) complexes with New Schiff base 3-[(Z)–5-Amino–1,3,3-Trimethyl Cyclohexylmethylimino]–1,3-Dihydroindol–2-One and determine their antimicrobial and antihelmentic activity¹⁰⁸. Ramadoss Gomathi, Andy RamuAthappan Murugan, were synthesized Cu(II), Co(II) and Ni(II) complexes with N-benzyl isatin Schiff base and investigated  their effect on Cancer Cell lines¹⁰⁹. Ahlam Jameel Abdulghani, Rasha Khuder Hussain were synthesized Co(II), Ni(II), Cu(II), Cd(II), Pd(II) and Pt(IV) with Schiff base Derived from Cefotaxime with 1H-indole-2,3-dione (Isatin) and 4-N,N-dimethyl-aminobenzaldehyde¹¹⁰. Mostafa K. Rabia, Ahmad Desoky M were synthesized Some Ni(II) Complexes with Isatin-Hydrazones and determined their physiochemical property¹¹¹. Md.Kudrat-E-Zahan et al were synthesized a novel bis imine Schiff base ligand derived from isatin and diethylene triamine and investigate their antimicrobaial activity¹¹².

 

Fig: Schematic diagram for antibacterial activity and DNA interaction of the investigated complexes

 

5. CONCLUSION:

Schiff bases derived from isatin and thiosemicarbazide and their metal complexes are one of the most important chemical classes of compounds having a common integral feature of a variety structural diversity and of active medicinal agents. This review reflects the contribution of Schiff bases to the design and development of novel lead having potential biological activities with fewer side effects. This bioactive core has maintained the interest of researchers in gaining the most suggestive and conclusive access in the field of various Schiff bases of medicinal importance from last decades. The present paper is an attempt to review all the biological activities reported for Schiff bases and their metal complexes derived from isatin and thiosemnicarbazide in the current literature with an update of recent research findings.

 

6. ACKNOWLEDGEMENT:

The authors are thankful to the Science and Technology Ministry of Bangladesh for providing their financial support. We also like to thanks to the Chairman, Department of Chemistry, University of Rajshahi, Rajshahi-6205, Bangladesh for laboratory support.

 

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Received on 04.12.2016         Modified on 23.12.2016

Accepted on 30.12.2016         © AJRC All right reserved