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ABSTRACT:
Anti metabolite cytarabine is fantastic molecule posses both of most important therapeutic action anti neoplastic and anti viralagent. Today the both of anti cancer and anti viral agent sharing the same therapeutic problems which limit their therapeutic pharmacological biological action which are (the resistance and the cytotoxicity and poor pharmacokinetics parameters). In our project we do the pharmaceutical chemical modifications on the cytarabine as nucleus and targeting amino functionality to design and synthesis the number of new derivatives in light of an pharmaceutical amino group prodrug modification strategies an imine formation to improve therapeutic action (antineoplastic and antiviral action), expected to explore new biological actionand to minimized the emergent resistance, cytotoxicity and expected to improve kinetics of cytarabine.
KEYWORDS: Anti Cancer, Cytarabine,I mine, Prodrug.
INTRODUCTION:
Cytarabine, is cytosine arabinoside (ara-C), is a chemotherapeutic agent used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), non-Hodgkin's lymphoma, and chronic myelogenous leukemia (CML). It is administered via injection, under the skin, or into the cerebrospinal fluid. There is a pharmaceutical liposomal formulation for which there is tentative evidence of enhanced outcomes in lymphoma including the meninges[1].
An antiviral therapeutic use of cytarabine is in the treatment of herpetic keratitis, herpes zoster (shingles) and viral infections that is resistant toidoxuridine[2]. Cytarabine-5'-triphosphate acts by inhibiting viral DNA synthesis.[3]
The power of cytarabine molecule as it to generate the targeting pharmacologic - therapeutic action as anti cancer and antiviral is extensively restricted and highly limited due to their an emergent resistance that developing as soon as administration of cytarabine resulting in abolish it is action. The cytarabine an emergent resistance is rationalized by a list number of mechanism related to it is pharmacological action included: Resistance can occur due toof decreased activation or transport and elevated catabolic breakdown. Metabolic degradation within the GI tract give rise to poor bioavailability. The drug distributes rapidly thought the tissues and total body water with cerebrospinal fluid (CSF) levels reaching) 20% to 40%) of those in plasma.
Cytidine deaminase is the main catabolic enzyme responsible for the inactivation of cytarabine in the serum into the inactive uracilform.[4] Cytarabine-5'monophosphate is deaminated via deoxycytidylate deaminase enzyme, producing the inactive uridine-5'monophosphate analog.[5] Cytarabine-5'-triphosphate is a substrate for SAMDH1(SAM and HD domain involving deoxynucleoside triphosphate...