Benzothienoquinolines, N-10 bioisosteres of cryptolepine as novel antiifectives with lower cytotoxicity

MEDI 328

Seth Y. Ablordeppey, seth.ablordeppey@famu.edu, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, Xue Y. Zhu, Xue.Zhu@famu.edu, Basic Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, Melissa Jacob, Research Institute of Pharmaceutical Sciences, University of Mississippi, The National Center for the Development of Natural Products, University, MS 38677, Shabana I. Khan, National Center for Natural Products Research, The University of Mississippi, School of Pharmacy, University, MS 38677, and Larry A. Walker, lwalker@olemiss.edu, National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677.
Previous studies on the indoloquinoline alkaloid, cryptolepine revealed that it has anti-bacterial, antifungal, antiprotozoal and anticancer activities. Limited Structure-Activity Relationship (SAR) studies on cryptolepine analogs revealed that modifications on the quindoline structure and substitution on the tetracyclic ring often led to significant changes in biological activity. The main objective of this study was to conduct a more extended SAR studies by the design, synthesis and evaluation of biological properties of agents resulting from isosteric replacement of the N-10 atom. Preliminary results indicate that, benzothienoquinolines constitute new anti-infectives with lower cytotoxicity than cryptolepine. The design, synthesis and antiinfective activities of some representative agents will be presented.

This research was supported in part by the Pharmaceutical Research Center NIH/NCRR grant 1 C06 RR12512-01 and by the Division of Research Resources, RCMI # G12 RR 03020. The research is also supported by NIGMS MBRS program, Grant # GM 08111 and a Title III award to SYA.

 

General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006