Sushma Reddy Gundala

Publications of Sushma Reddy Gundala

• Second generation benzofuranone ring substituted noscapine analogs: synthesis and biological evaluation.

  Authors: Ram Chandra Mishra, Prasanthi Karna, Sushma Reddy Gundala, Vaishali Pannu, Richard A Stanton, Kamlesh Kumar Gupta, M Hope Robinson, Manu Lopus, Leslie Wilson, Maged Henary, Ritu Aneja

  Biochemical pharmacology. 07/2011; 82(2):110-21.

  Microtubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas areMicrotubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems. Noscapinoids represent an emerging class of microtubule-modulating anticancer agents based upon the parent molecule noscapine, a naturally occurring non-toxic cough-suppressant opium alkaloid. Here we report in silico molecular modeling, chemical synthesis and biological evaluation of novel analogs derived by modification at position-7 of the benzofuranone ring system of noscapine. The synthesized analogs were evaluated for their tubulin polymerization activity and their biological activity was examined by their antiproliferative potential using representative cancer cell lines from varying tissue-origin [A549 (lung), CEM (lymphoma), MIA PaCa-2 (pancreatic), MCF-7 (breast) and PC-3 (prostate)]. Cell-cycle studies were performed to explore their ability to halt the cell-cycle and induce subsequent apoptosis. The varying biological activity of these analogs that differ in the nature and bulk of substituent at position-7 was rationalized utilizing predictive in silico molecular modeling.

• The first low microM SecA inhibitors.

  Authors: Weixuan Chen, Ying-ju Huang, Sushma Reddy Gundala, Hsiuchin Yang, Minyong Li, Phang C Tai, Binghe Wang

  Bioorganic & medicinal chemistry. 02/2010; 18(4):1617-25.

  SecA ATPase is a critical member of the Sec family, which is important in the translocation of membrane and secreted polypeptides/proteins in bacteria. Small molecule inhibitors can be very usefulSecA ATPase is a critical member of the Sec family, which is important in the translocation of membrane and secreted polypeptides/proteins in bacteria. Small molecule inhibitors can be very useful research tools as well as leads for future antimicrobial agent development. Based on previous virtual screening work, we optimized the structures of two hit compounds and obtained SecA ATPase inhibitors with IC(50) in the single digit micromolar range. These represent the first low micromolar synthetic inhibitors of bacterial SecA and will be very useful for mechanistic studies.