1. INTRODUCTION
Thiosemicarbazone is a derivative of imine which is formed when an aldehyde/ketone reacts with a thiosemicarbzide through a condensation reaction. The presence of the hetero atoms like Sulphur and Nitrogen makes these derivatives biologically active. Lately, great emphasis is laid on the synthesis and development of these derivatives reason being the wide variety of pharmacological activities exhibited by them. So far, thiosemicarbazones have been shown to exhibit analgesic and anti inflammatory [1], antibacterial [2],anticancer [3] anticonvulsant [4] anti fungal [5], anti HIV [6], anti leishmaniac [7], anti-malarial[8] neurotropic [9], anti trypanosomal [10], antitubercular [11] and antiviral [12] activities. Few thiosemicarbazone …show more content…
It is a group of diseases involving abnormal cell proliferation may or may not having the potential to invade other parts of the body as well.[20]. There are more than 100 types of cancer known so far which can affect the human population [21]. Thus it is evident that no single drug can be as efficient to treat all forms of cancer. Many drugs are now available as chemotherapeutic agents against various forms of cancer, however they also possess serious side effects while few others have been rendered inactive due to emergence of resistance against them. Thus the need to develop new antineoplastic agents with better efficacy and lower toxicity profile will always be there. Many new moieties were studied for their pharmacological potential against combatting cancers and thiosemicarbazones have been one of them. In 1960s it was found that these molecules possess significant activity and can be exploited further [3]. Since then, these molecules received due attention and in recent years one of them, Triapine® (3-aminopyridine2-carboxaldehyde thiosemicarbazone), has been developed as an anticancer drug [22]. Owing to its activity this molecule has made to the phase II of the clinical trials …show more content…
In contrast to other drug molecules wherein P-gp sequestration renders the drug unavailable for action, lysosomal P-gp enhanced the transport of thiosemicarbazones into the lysosomes. [28]. This accounted for the increased lysosomal damage and cytotoxicity of thiosemicarbazones towards P-gp expressing tumor cells.[28]
3.3 Inhibition of Metastasis :Metastasis accounts for the maximum deaths due to cancer. NDRG1 (N-Myc downstream regulated gene 1) is a metastasis suppressor protein [30,31]. It inhibits primary tumor growth, angiogenesis, and metastasis [32-34]. Thiosemicarbazones were found to upregulate the NDRG1 protien by depleting the iron from tumor cells resulting in a state of hypoxia. [35,36]
This article covers the works and results of development of thiosemicarbazones as antitumor agents carried out in last ten years.
Thiosemicarbazone is a derivative of imine which is formed when an aldehyde/ketone reacts with a thiosemicarbzide through a condensation reaction. The presence of the hetero atoms like Sulphur and Nitrogen makes these derivatives biologically active. Lately, great emphasis is laid on the synthesis and development of these derivatives reason being the wide variety of pharmacological activities exhibited by them. So far, thiosemicarbazones have been shown to exhibit analgesic and anti inflammatory [1], antibacterial [2],anticancer [3] anticonvulsant [4] anti fungal [5], anti HIV [6], anti leishmaniac [7], anti-malarial[8] neurotropic [9], anti trypanosomal [10], antitubercular [11] and antiviral [12] activities. Few thiosemicarbazone …show more content…
It is a group of diseases involving abnormal cell proliferation may or may not having the potential to invade other parts of the body as well.[20]. There are more than 100 types of cancer known so far which can affect the human population [21]. Thus it is evident that no single drug can be as efficient to treat all forms of cancer. Many drugs are now available as chemotherapeutic agents against various forms of cancer, however they also possess serious side effects while few others have been rendered inactive due to emergence of resistance against them. Thus the need to develop new antineoplastic agents with better efficacy and lower toxicity profile will always be there. Many new moieties were studied for their pharmacological potential against combatting cancers and thiosemicarbazones have been one of them. In 1960s it was found that these molecules possess significant activity and can be exploited further [3]. Since then, these molecules received due attention and in recent years one of them, Triapine® (3-aminopyridine2-carboxaldehyde thiosemicarbazone), has been developed as an anticancer drug [22]. Owing to its activity this molecule has made to the phase II of the clinical trials …show more content…
In contrast to other drug molecules wherein P-gp sequestration renders the drug unavailable for action, lysosomal P-gp enhanced the transport of thiosemicarbazones into the lysosomes. [28]. This accounted for the increased lysosomal damage and cytotoxicity of thiosemicarbazones towards P-gp expressing tumor cells.[28]
3.3 Inhibition of Metastasis :Metastasis accounts for the maximum deaths due to cancer. NDRG1 (N-Myc downstream regulated gene 1) is a metastasis suppressor protein [30,31]. It inhibits primary tumor growth, angiogenesis, and metastasis [32-34]. Thiosemicarbazones were found to upregulate the NDRG1 protien by depleting the iron from tumor cells resulting in a state of hypoxia. [35,36]
This article covers the works and results of development of thiosemicarbazones as antitumor agents carried out in last ten years.