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|Title:||A theoretical investigation into the origin of antitumour activities of several derivatives of 25diphenyl furan system and development of some requisite modelling software|
|Abstract:||This thesis discusses a set of theoretical investigations performed on the DNA-binding characteristics of various diamidine derivatives of 2,5-diphenyl furan, an emerging class of potent drugs having anti-tumour and anti-microbial activity, and with such pharmacological actions arising out of their binding with cell DNA. Details about the investigations carried out are discussed in eight chapters as delineated below. Figure: Two of the investigated drugs DB60 and DB75 with their modelled DNA-bound forms Chapter 1 A general introduction to the available background knowledge on DNA minor-groove binding drugs, with emphasis on the investigated class of drugs, is presented in this chapter. The diarylfuran diamidine drugs, which are diamidine derivatives of diaryl-substituted furan, constitute a promising class of drugs with strong anti-parasitic, anti-bacterial and anti-tumour action. It has been established that they exert all kinds of their therapeutic actions by virtue of their AT-specific binding at the minor groove of DNA via hydrogen bonds and other donor-acceptor interactions as well as via utilisation of shape recognition, thereby causing to inhibit DNA replication. Out of them, the dicationic diamidine derivatives of 2,5-diphenylfuran constitute an important class of the diarylfurans, with potent drugs such as DB75 (furimidazoline) with strong anti-parasitic and anti-bacterial activity, and DB60 (furimidazoline) with significant anti-tumour activity. So the objective of this study is to perform theoretical investigation about DNA binding characteristics of this class of drugs. Ten prototype members namely DB60, DB75, DB181, DB226, DB244, DB249, DB569, DB820, DB829 and DB867 of this class were chosen for study, based on their reported experimentally observed biological activity. Their interactions with the AT base pair and with AT-rich oligonucleotides is proposed to be studied by ab initio methods and by force field studies, so as to provide better understanding of their DNA-binding behaviour, which is...|
|Appears in Departments:||Department of Chemistry|
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