Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo

P. Vijaya Babu; Soumita Mukherjee; Girdhar Singh Deora; Keerthana Sarma Chennubhotla; Raghavender Medisetti; Swapna Yellanki; Pushkar Kulkarni; Shivashankar Sripelly; Kishore V. L. Parsa; Kiranam Chatti; K. Mukkanti; Manojit Pal

doi:10.1039/C3OB41504J

Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo†

P. Vijaya Babu,^ab Soumita Mukherjee,^a Girdhar Singh Deora,^a Keerthana Sarma Chennubhotla,^ac Raghavender Medisetti,^ac Swapna Yellanki,^ac Pushkar Kulkarni,^ac Shivashankar Sripelly,^a Kishore V. L. Parsa,^a Kiranam Chatti,^a K. Mukkanti^b and Manojit Pal*^a

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^a Dr Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India
E-mail: manojitpal@rediffmail.com
Tel: +91 40 6657 1500

^b Chemistry Division, Institute of Science and Technology, JNT University, Kukatpally, Hyderabad 500072, India

^c Zephase Therapeutics (an incubated company at the DRILS), University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India

Abstract

A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC₅₀ ≈ 5–14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.

Organic & Biomolecular Chemistry

Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo†

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Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo

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