Synthesis of 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives: their evaluation as potential PDE 4B inhibitors possessing cytotoxic properties against cancer cells.
The 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives were designed as potential inhibitors of PDE4B. These compounds were synthesized via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required alkynes were prepared from nimesulide via N-propargylation and then nitro group reduction followed by a CAN mediated modified Skraup reaction of the resulting amine. All the synthesized compounds showed PDE4B inhibitory properties in vitro at 30μM with two compounds showing >50% inhibition that were supported by the in silico docking results of these compounds at the active site of PDE4B. Three of these PDE4 inhibitors showed promising cytotoxic properties against A549 human lung cancer cells in vitro with IC50 ∼8-9μM.
Department of Chemistry, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India.
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Praveena
MSN Pharmachem Pvt. Ltd., Plot No. 212/A,B,C,D, APIICL, Phase-II, Pashamylaram, Patancheru (M), Medak District 502 307, Andhra Pradesh, India.
Shylaprasad
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Durgadas
Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
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Suresh Babu
Chemical Biology Laboratory, Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
Surekha
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Akkenapally
Chemical Biology Laboratory, Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
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Ganesh Kumar
The University of Queensland, School of Pharmacy, Brisbane, QLD 4072, Australia.
Girdhar Singh
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Deora
Department of Chemistry, School of Engineering, Anurag Group of Institutions, R.R.District 501301, Andhra Pradesh, India.
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Murthy
Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
Khagga
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Mukkanti
Department of Chemistry, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India. Electronic address: sarbani277@yahoo.com.
Sarbani
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D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry* / Q000378:metabolism; D061565:Cycloaddition Reaction; D006801:Humans; D062105:Molecular Docking Simulation; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000480:Alkynes; D001386:Azides; D058988:Phosphodiesterase 4 Inhibitors; D014230:Triazoles; D003300:Copper; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4
1,2,3-Triazole; Cycloaddition; Cytotoxic activities; Nimesulide; PDE4B