SEMICARBAZONE: A VERSATILE THERAPEUTIC ANALOGUE AND IT`S PHARMACOLOGICAL EVALUATION
Tripti Verma*, Chandra Shekhar Sharma, HemendraPratap Singh
Bhupal Nobles’ College of Pharmacy,
Udaipur, Rajasthan, India
Semicarbazones are compounds which are synthesized by a condensation reaction between a ketone or aldehyde and semicarbazide. Semicarbazone have biological activity against many of the most common species of bacteria. The biological properties of semicarbazonesare often related to metal ion coordination. The literature survey revealed that semicarbazones had been emerged as a compound with broad range of activities including anti-fungal, anti-bacterial, anticonvulsant, anticancer, antimicrobial activity and anti-inflammatory activity. Semicarbazone also used as ligand as the cytotoxic agent, spectrophotometric agents as well for the analysis of metal ions and in qualitative organic analysis of carbonyl compounds. In the present study we have focused on the Pharmacological evaluation of semicarbazone analogues. As per activity there are different Pharmacological evaluation methods of synthesized compound.
REFERENCE ID: PHARMATUTOR-ART-1934
A semicarbazone is a derivative of imines formed by a condensation reaction between a ketone or aldehyde and semicarbazide. They are classified as imine derivatives because they are formed from the reaction of an aldehyde or ketone with the terminal -NH2 group of semicarbazide, which behaves very similarly to primary amines.The semicarbazide which are the raw material of semicarbazone have been known to have biological activity against many of the most common species of bacteria (Dorgan et al., 1999)1.Semicarbazone, themselves are of much intrest due to a wide spectrum of anti-fungal and anti-bacterial activities (Singhal and Paul 2011a)2. Recently some researcher had reviewed of bioactivity of semicarbazones and they have exhibited anti-convulsant (Pandeyaet al., 2000)3, anti-tubercular (Sriramet al., 2004)4, anti-oxidant (Singhal and Paul 2011b)5, anti-microbial, analgesic, anti-pyretic (Singhal and Paul 2011c)6 and anti-inflammatory activity (Singh et al., 2010)7.
In organic chemistry, semicarbazone is a derivative of semicarbazide which contains an additional ketone functional group.
Figure 1: General Structure of semicarbazone analogues
Dimmocket al., reported an extensive series of semicarbazone8. The lead compound amongthe (aryloxyl) arylsemicarbazones was 4-(4-fluorophenoxy) benzaldehydesemicarbazone.Preclinical evaluations have been completed and an (IND) has been filed. The compound is apotent sodium channel blocker (Na+) and it is planned to be developed for the treatment ofneuropathic pain. Phase I Clinical trials are scheduled in the near future.
The semicarbazone is formed when ammonia related a compound (nucleophiles) such assemicarbazide is added to the carbonyl group (=CO), they form imine like derivatives (Fig.2).
Figure 2: Synthesis of semicarbazone analogues
The conversion of aldehydes and ketones into imine like derivatives is an exothermic and pH dependent reaction.
General method for the synthesis of semicarbazone analogues
The general method for the synthesis of semicarbazone analogues is presented in Figure 3.
Figure 3: General method for the synthesis of semicarbazone analogues
Applications of semicarbazones and their complexes:
The metal complexes of semicarbazones play an essential role in agriculture, pharmaceutical and industrial chemistry and they are used as catalysts, in various biological systems, polymers and dyes, besides some uses antifertility and enzymatic agents. The biological properties of semicarbazonesare often related to metal ion coordination. Firstly, lipophilicity, which controls the rate of entry in to the cell, is modified by coordination8. Also, the metal complex can be more active than the free ligand. The mechanism of action can involve binding to a metal in vivo or the metal complex may be a vehicle for activation of the ligand as the cytotoxic agent. Moreover, coordination may lead to significant reduction of drug-resistance9. They are also used as spectrophotometric agents as well for the analysis of metal ions10 and are frequently used in the qualitative organic analysis of carbonyl compounds11.
Recently, thiosemicarbazones have been synthesized and screened against the three parasitic cysteine proteases cruzain, falcipain-2, and rhodesainand against their respective parasite sources, Trypanosomacruzi, Plasmodiumfalciparium, and Trypanosoma brucei12. The results obtained suggested that thiosemicarbazones represent validated leads that kill several species of protozoan parasites through the inhibition of cysteine proteases as well as through action against other targets. Furthermore, semicarbazones, which can also be regarded as urea derivatives, have gained considerable importance13in recent years in the design of enzyme inhibitors14, as replacement for the amide (–CO–NH–) bond in peptidomimetics15.
Anti-Fungal and anti-bacterial activity:
Micrbial resistance towards drug creates a very serious problem since last 3 decades because of this development of resistance many drug are now useless which were very effective (Cohen 1992; Cunha 1998)16,17. Moreover, the toxic effect produced by these anti-biotic is also reducing their significance. So, for the need for new anti-microbial is always being there. Anti-fungal screening of synthesised chalconesemicarbazone derivative was conducted using a filter paper disc method.
The synthesised compound were screened for their anti-fungal activity against four fungi, Candidaalbicans, Aspergillusniger, Asperillusorzane, Penicilliumcitrinum at 100 ug ml-1involving disc diffusion method with saburoud dextrose agar (Hi-media).
The synthesized compound were screened for their anti-bacterial activity against two gram positive (Bacillus subtilis, Micrococusluteus) and two gram negative (Klebsiellaaerogenes, Salmonella paratyphi) bacteria at 100 ug/ml involving disc diffusion method with Mueller- Hinter agar media (Hi-media)18,19. Anti-bacterial activity determined by measuring zone inhibition of in millimetre around each of the disc and compared with standard Ciprofloxacin (100 ug/ml). Anti-bacterial activity was classified as Standard (>27 mm) Highly active (21-27 mm), moderately active (15-21 mm), least active (12-15 mm) and less than 12 mm was taken as inactive20.
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