Title of Thesis
Combinatorial Design, Synthesis, Bioevaluation
and SAR Studies on Some Small Drug]like Molecular Libraries
Department of Chemistry / Quaid]i]Azam
|Number of Pages|
|Keywords (Extracted from title, table of contents and
abstract of thesis)|
Drug]like, Libraries, Amino,
Antitumor, Bioevaluation, Molecular, Combinatorial, Rationale,
synthesis of small libraries of a variety of amino chalcones has
been carried out in solution phase under standard Claisen Schmidt
conditions. The compounds were tested for their potential as
antibacterial and cytotoxic agents as well as phosphatase inhibitors
and the leads were identified in each bioassay. Chalcone 7 was found
to have strongest potential as cytotoxic agent, while chalcone 11 be
the most potent PGM inhibitory agent.
Parallel synthesis of a 120 member chalcone library was carried out
as mixture synthesis following the positional scanning protocol. The
identification of lead in this library was carried out by
deconvulution and chalcones 22 and 41 were found to be the most
potential candidates to be developed as antibacterial agents.
Following the same strategy of mixture synthesis, another 175 member
chalcones library was synthesized and most potent anticancer
chalcones 31, 61 and 78 were identified by deconvolution through
position scanning protocol.
Peptidyl α,β- unsaturated ketones were synthesized as novel bis-
electrophiles susceptible for 3+2 and 3+4 annulations. As a result,
peptidyl oxazoles, pyrazolines, pyrazoles, benzothiazepines and
benzodiazepines were synthesized.
Potent antidiabetic chalcones were docked into the PGM active site
and a rationale was found for greater antidiabetic activity of
chalcones over the other. Rational design and synthesis of some
cytotoxic chalcones was based on 3DQSAR studies using CoMFA as a
tool. 3DQSAR studies were also carried out on a library of 30
chalcones as potential antitumor agents.