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Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors.
Bioorg Chem 2019; 93:103314BC

Abstract

A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 < 2.5 μM) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase.

Authors+Show Affiliations

School of Chemical Sciences and Pharmacy, Central University of Rajasthan NH-8, Bandarsindri, Ajmer 305817, Raj, India.Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151001, Punjab, India.Laboratory of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151001, Punjab, India.Natural Product Chemistry and Process Development Division, CSIR-IHBT, Palampur, Himachal Pradesh 176061, India.Natural Product Chemistry and Process Development Division, CSIR-IHBT, Palampur, Himachal Pradesh 176061, India.Laboratory of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151001, Punjab, India.Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151001, Punjab, India. Electronic address: raj.khunger@gmail.com.Laboratory of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151001, Punjab, India. Electronic address: sandeepsingh82@gmail.com.School of Chemical Sciences and Pharmacy, Central University of Rajasthan NH-8, Bandarsindri, Ajmer 305817, Raj, India. Electronic address: dms@curaj.ac.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31590041

Citation

Ansari, Arshad J., et al. "Exploration of Pd-catalysed Four-component Tandem Reaction for One-pot Assembly of Pyrazolo[1,5-c]quinazolines as Potential EGFR Inhibitors." Bioorganic Chemistry, vol. 93, 2019, p. 103314.
Ansari AJ, Joshi G, Yadav UP, et al. Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors. Bioorg Chem. 2019;93:103314.
Ansari, A. J., Joshi, G., Yadav, U. P., Maurya, A. K., Agnihotri, V. K., Kalra, S., ... Sawant, D. M. (2019). Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors. Bioorganic Chemistry, 93, p. 103314. doi:10.1016/j.bioorg.2019.103314.
Ansari AJ, et al. Exploration of Pd-catalysed Four-component Tandem Reaction for One-pot Assembly of Pyrazolo[1,5-c]quinazolines as Potential EGFR Inhibitors. Bioorg Chem. 2019 Sep 26;93:103314. PubMed PMID: 31590041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors. AU - Ansari,Arshad J, AU - Joshi,Gaurav, AU - Yadav,Umesh Prasad, AU - Maurya,Antim K, AU - Agnihotri,Vijai K, AU - Kalra,Sourav, AU - Kumar,Raj, AU - Singh,Sandeep, AU - Sawant,Devesh M, Y1 - 2019/09/26/ PY - 2019/05/15/received PY - 2019/08/12/revised PY - 2019/09/24/accepted PY - 2019/10/8/pubmed PY - 2019/10/8/medline PY - 2019/10/8/entrez KW - Anticancer KW - Catalysis KW - Drug discovery KW - EGFR KW - Molecular modelling KW - Pyrazolo[1,5-c]quinazolines SP - 103314 EP - 103314 JF - Bioorganic chemistry JO - Bioorg. Chem. VL - 93 N2 - A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 < 2.5 μM) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/31590041/Exploration_of_Pd-catalysed_four-component_tandem_reaction_for_one-pot_assembly_of_pyrazolo[1,5-c]quinazolines_as_potential_EGFR_inhibitors L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(19)30785-0 DB - PRIME DP - Unbound Medicine ER -