Titanocene anticancer complexes and their binding mode of action to human serum albumin: a computational study

Due to the pivotal role played by human serum albumin (HSA) in the transport and cytotoxicity of titanocene complexes, a docking study has been performed on a selected set of titanocene complexes to aid in the current understanding of the potential mode of action of these titanocenes upon binding HSA. Analysis of the docking results has revealed potential binding at the known drug binding sites in HSA and has provided some explanation for the specificity and subsequent cytotoxicity of these titanocenes. Additionally, a new alternative binding site for these titanocenes has been postulated

Computational simulation technique : computational studies and molecular modelling of proteins coordinated by metal-based chemotherapeutic agents

Research in the field of titanium-based complexes as potential anticancer drugs has led to impressive results in vitro, but there is still scope for further improvements. Significant effort has been put into synthetic research and biological evaluation of titanocene derivatives, as well as the identification of their main biological targets. Surprisingly, the area of computer-aided drug design (CADD) has not been utilized up-to-date for the design of novel titanium-based compounds. The work within the thesis describes the computational approaches employed to study the mode of action of titanium-based anticancer agents, highlighting the structural features required for biological activity. Consequently, novel titanium-based derivatives were designed and synthesized. Furthermore, the synthetic attempts for amidosilyl-substituted titanocene and ferrocene derivatives with potentially enhanced activity are also reported. The first chapter provides a thorough introduction into the developments in the field of metal-based antitumour agents with a particular emphasis on titanium-based agents and assessment of their cytotoxic activity. Chapter 2 describes the first systematic receptor- based docking approach utilized to understand the binding mode of titanium-based agents against human serum albumin (RSA). The first 3D-QSAR study, which is reported in Chapter 3, was performed on a series of titanocene complexes to gain insight into the key structural features vital for their biological activity and to advance the design of potent titanocene anticancer agents. The successful synthesis of six novel benzyl-substituted titanocene derivatives, which have been designed based on the 3D-QSAR analysis is described in Chapter 4. Chapter 5 focuses on the attempts made for the synthesis of a range of amidosilyl-substituted titanium and iron-based metallocenes. Although the amidosilyl- substituted derivatives could not be obtained as pure compounds, six titanium and iron- based metallocenes were successfully synthesized. Chapter 6 summarizes the results obtained and provides suggestions for areas of future research.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Synthesis, Characterization and Preliminary Anti-inflammatory Evaluation of New Etodolac Derivatives

Three new hydrazone derivatives of Etodolac were synthesized and evaluated for their anti-inflammatory activity by using egg white induced paw edema method. All the synthesized target compounds were characterized by CHN- microanalysis, FT-IR spectroscopy, and 1HNMR analysis. The synthesis of the target (P1-P3) compounds was accomplished following multistep reaction procedures. The synthesized target compounds were found to be active in reducing paw edema thickness and their anti-inflammatory effect was comparable to that of the standard (Etodolac)