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|Title:||QSAR with electrotopological state atom index:Part II†-Antimalarial activity of dihydroqinghaosu derivatives‡|
Pal, Dipak Kumar
|Abstract:||QSAR analysis of antimalarial activity of some ester and ether derivatives (AR1-AR21) of dihydroqinghaosu (dihydroartemisinin) has been done with electrotopological state atom (ETSA) index in an attempt to explore the atoms or fragments of the molecules that are most important for the mediation of the activity. The study reveals the importance of the oxygen atoms (including those of the peroxide bridge) of artemisinin skeletal ring structure and the lactol oxygen. The observation corroborates an earlier finding that reduction of the peroxide bridge of artemisinin resulting in loss of one oxygen reduces the activity. It was previously suggested that artemisinin and related compounds might kill the parasites by a free radical mediated process and the peroxide bridge might play a crucial role in the mechanism. Further, that the dihydro form (of the lactone moiety) of artemisinin is more active is also traced to the importance of the corresponding lactol oxygen atom in the present QSAR study. Thus, diagnostic potential of the ETSA scheme in identifying the atoms or fragments important for activity is revealed from the study. The study further suggests that α configuration of the lactol oxygen is preferred. The ether / ester side chain should be of less bulk and preferably with oxo functionality. Presence of branchedness and alicyclic ring in the side chain has negative contributions to the activity.|
|Appears in Collections:||IJC-B Vol.40B(07) [July 2001]|
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