TY - JOUR
T1 - Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents
T2 - A Structure-Activity Relationship Study
AU - Rana, Sandeep
AU - Blowers, Elizabeth C.
AU - Tebbe, Calvin
AU - Contreras, Jacob I.
AU - Radhakrishnan, Prakash
AU - Kizhake, Smitha
AU - Zhou, Tian
AU - Rajule, Rajkumar N.
AU - Arnst, Jamie L.
AU - Munkarah, Adnan R.
AU - Rattan, Ramandeep
AU - Natarajan, Amarnath
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/5/26
Y1 - 2016/5/26
N2 - Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-ΰB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-ÎM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents.
AB - Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-ΰB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-ÎM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents.
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U2 - 10.1021/acs.jmedchem.6b00400
DO - 10.1021/acs.jmedchem.6b00400
M3 - Article
C2 - 27077228
AN - SCOPUS:84971673253
SN - 0022-2623
VL - 59
SP - 5121
EP - 5127
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 10
ER -