2.1 Biological activities of Thiosemicarbazide
In a study by Šarkanj, Molnar, ?a?i?, & Gille (2013), thiosemicarbazides have shown good antioxidant activity, with galvinoxyl radical scavenging activity higher than 80%, better than thiazolidinones with same subtituent. However, in the same study found that the antifungal activity of thiosemicarbazide is lower than thiazolidinones.

Zhang et al (2017) has synthesized derivatives of thiosemicarbazide containing piperidine fragments and found its antifungal acitivity on Pythium aphanidermatum, Rhizoctonia solani, Valsa mali and Gaeu-mannomyces graminis. A derivative with substituent 5-Chloro-2-hydroxybenzylidene showed highest inhibition against P. aphanidermatum with similar activity to a commercial fungicide called Fluopicolide.

A study by Plech, Wujec, Siwek & Malm (2010) demonstrated that thiosemicarbazide derivatives with Mannich bases showed beter antibacterial activity compared to s-triazoles studied in the experiment. The study also showed that thiosemicarbazide derivatives which contain an unsubstituted phenyl ring had low antimicrobial effect against Gram-positive bacteria. Compounds with substituted phenyl ring on para isomers have showed better activity compared to their ortho isomers; showing that the para position is more beneficial for electron-withdrawing properties.

Studies in organometallics have found that thiosemicarbazide can act as anticorrosive agent and can increase adsorbance of grafted walls. Hossain & Almarshad (2006) demonstrated that when thiosemicarbazide is added to acid, it increases the E_corr of steel and reduces I_corr of the acid, resulting to reducing the corrosion rate of carbon steel in sulphuric acid. Zhang (2013) demonstrated that modified multiwalled carbon nanotubes with thiosemicarbazides (MWCNTs-TB) have better dispersibility compared to pristine modified multiwalled carbon nanotubes (MWCNTs).

2.2 Effect of substituents and ligands on activity of compound
Synthesis of new TSC derivatives involves addition of substituents and chelation with transitional metal ions to form new complexes. The activities of these complexes are highly dependent on the form of the thiosemicarbazide moiety, nature of the choloraromatic ring, and position of attachment to the ring. By having different groups of elements as substituents will produce different activities of the compound with different affinity and efficacy. In regards to affinity, complexes that have higher affinity towards microbial activity will have lesser cytotoxic activity.

Cihan-Üstündag? et al. (2016) proved that presence free thiosemicarbazide moiety is important in synthesizing antiviral compounds. In the study, a derivative of thiosemicarbazide prepared for possible Coxsackie vaccine with substituents of ethyl substituent showed strong antiviral activity against the virus compared to its other derivatives with methyl, propyl and allyl substituent while the compound with bulkier substituent, (butyl or aromatic substituent), did not show any antiviral activity. This proves free thiosemicarbazide moiety plays an important role in giving antiviral properties to a compound. In regards to cytotoxic activity, the study found that bulkier derivatives showed higher activity compared to derivatives that possess antiviral activity.

Another study by Hussein, Iqbal, Umar, Haque, & Guan (2015) reported that thiosemicarbazone derivatives that have anticancer properties does not show cytotoxicity towards normal fibroblast cell lines. The study found that thiosemicarbazones with phenyl, dimethyl, and ethyl substituent showed anticancer activity towards pancreatic cell (PANC-1), breast cancer cells (MCF-7), and human colon cancer cells (HCT-116) with highest activity towards pancreatic cells. But the compounds showed no toxicity when tested on normal mouse fibrablast cell lines.

Soares et al. (2011) compared antiparasitic activity of thiosemicarbazone and semicarbazone against Trypanosoma cruzi and found that thiosemicarbazones showed better activity than semicarbazones. Soares et al. also explained that the difference in effectiveness is due to change of sulfur to oxygen in the compound.

A study by Pahontu et al. (2014) discussed that the chelation of thiosemicarbazide with metal ions will produce a complex with higher antibacterial acitvity. The study explained that the chelation cause a reduce in polarity of the metal ion which increases lipophilic properties of the compound and improves penetration into the cells of microorganisms. This property is desirable in pharmacology as to produce new drugs with lesser side effects.

2.3 Activities of other ligands and substituents in the compound
Betageri et al. (2005) stated that trifluoromethyl group may able to enhance its hydrogen bond donor ability by increasing the acidity of the central hydroxyl group in the molecule.

Nfor et al. (2013) reported that chelation of Nickel II with the hydrazole ligand increases the antifungal activity of the compound against A. flavus, A. niger and C. albicans.