Triple targeting of mutant EGFR^L858R/T790M, COX-2, and 15-LOX: design and synthesis of novel quinazolinone tethered phenyl urea derivatives for anti-inflammatory and anticancer evaluation

References

• Abdellatif KR, Fadaly WA, Mostafa YA, Zaher DM, Omar HA. Thiohydantoin derivatives incorporating a pyrazole core: design, synthesis and biological evaluation as dual inhibitors of topoisomerase-i and cycloxygenase-2 with anti-cancer and anti-inflammatory activities. Bioorg Chem. 2019;91:103132.
   PubMed Web of Science ®Google Scholar
• Hu L, Fan M, Shi S, Song X, Wang F, He H, Qi B. Dual target inhibitors based on EGFR: promising anticancer agents for the treatment of cancers (2017). Eur J Med Chem. 2022;227:113963.
   PubMed Web of Science ®Google Scholar
• Abdelazeem AH, El-Saadi MT, Said EG, Youssif BG, Omar HA, El-Moghazy SM. Novel diphenylthiazole derivatives with multi-target mechanism: synthesis, docking study, anticancer and anti-inflammatory activities. Bioorg Chem. 2017;75:127–138.
   PubMed Web of Science ®Google Scholar
• Gouda AM, Abdelazeem AH, Omar HA, Abdalla AN, Abourehab MA, Ali HI. Pyrrolizines: design, synthesis, anticancer evaluation and investigation of the potential mechanism of action. Bioorg Med Chem. 2017;25(20):5637–5651.
   PubMed Web of Science ®Google Scholar
• El-Sayed NA, Nour MS, Salem MA, Arafa RK. New oxadiazoles with selective-COX-2 and EGFR dual inhibitory activity: design, synthesis, cytotoxicity evaluation and in silico studies. Eur J Med Chem. 2019;183:111693.
   PubMed Web of Science ®Google Scholar
• Bhatia P, Sharma V, Alam O, Manaithiya A, Alam P, Alam MT, Imran M. Kahksha Novel quinazoline-based EGFR kinase inhibitors: a review focussing on SAR and molecular docking studies (2015–2019). Eur J Med Chem. 2020;204:112640.
   PubMed Web of Science ®Google Scholar
• Pawara R, Ahmad I, Nayak D, Wagh S, Wadkar A, Ansari A, Belamkar S, Surana S, Nath Kundu C, Patil C, et al. Novel, selective acrylamide linked quinazolines for the treatment of double mutant EGFR-l858R/T790M non-small-cell lung cancer (NSCLC). Bioorg Chem. 2021;115:105234.
   PubMed Web of Science ®Google Scholar
• Chen L, Zhang Y, Tian L, Wang C, Deng T, Zheng X, Wang T, Li Z, Tang Z, Meng Q, et al. Noncovalent EGFR T790M/L858R inhibitors based on diphenylpyrimidine scaffold: design, synthesis, and bioactivity evaluation for the treatment of NSCLC. Eur J Med Chem. 2021;223:113626.
   PubMed Web of Science ®Google Scholar
• Shaheen MA, El-Emam AA, El-Gohary NS. Design, synthesis and biological evaluation of new series of hexahydroquinoline and fused quinoline derivatives as potent inhibitors of wild-type EGFR and mutant EGFR (L858R and T790M). Bioorg Chem. 2020;105:104274.
   PubMed Web of Science ®Google Scholar
• Chen L, Zhang Y, Wang C, Tang Z, Meng Q, Sun H, Qi Y, Ma X, Li L, Li Y, et al. Design, synthesis, and biological evaluation of hydroxamic acid-substituted 2, 4-diaryl aminopyrimidines as potent EGFRT790M/L858R inhibitors for the treatment of NSCLC. Bioorg Chem. 2021;114:105045.
   PubMed Web of Science ®Google Scholar
• Elzahhar PA, Abd El Wahab SM, Elagawany M, Daabees H, Belal ASF, El-Yazbi AF, Eid AH, Alaaeddine R, Hegazy RR, Allam RM, et al. Expanding the anticancer potential of 1,2,3-triazoles via simultaneously targeting cyclooxygenase-2, 15-lipoxygenase and tumor-associated carbonic anhydrases. Eur J Med Chem. 2020;200:112439.
   PubMed Web of Science ®Google Scholar
• Gouda AM, Beshr EA, Almalki FA, Halawah HH, Taj BF, Alnafaei AF, Alharazi RS, Kazi WM, AlMatrafi MM. Arylpropionic acid-derived NSAIDS: new insights on derivatization, anticancer activity and potential mechanism of action. Bioorg Chem. 2019;92:103224.
   PubMed Web of Science ®Google Scholar
• Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 2002;94(4):252–266.
   PubMed Web of Science ®Google Scholar
• Afifi OS, Shaaban OG, Abd El Razik HA, Shams El-Dine SE-DA, Ashour FA, El-Tombary AA, Abu-Serie MM. Synthesis and biological evaluation of purine-pyrazole hybrids incorporating thiazole, thiazolidinone or rhodanine moiety as 15-LOX inhibitors endowed with anticancer and antioxidant potential. Bioorg Chem. 2019;87:821–837.
   PubMed Web of Science ®Google Scholar
• Omar YM, Abdel-Moty SG, Abdu-Allah HH. Further insight into the dual COX-2 and 15-LOX anti-inflammatory activity of 1,3,4-thiadiazole-thiazolidinone hybrids: the contribution of the substituents at 5th positions is size dependent. Bioorg Chem. 2020;97:103657.
   PubMed Web of Science ®Google Scholar
• Ghanim AM, Rezq S, Ibrahim TS, Romero DG, Kothayer H. Novel 1,2,4-triazine-quinoline hybrids: the privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition. Eur J Med Chem. 2021;219:113457.
   PubMed Web of Science ®Google Scholar
• Rao CV, Janakiram NB, Madka V, Devarkonda V, Brewer M, Biddick L, Lightfoot S, Steele VE, Mohammed A. Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma. Oncotarget. 2015;6(32):33290–33305.
   PubMedGoogle Scholar
• Mohammed A, Janakiram NB, Pant S, Rao CV. Molecular targeted intervention for pancreatic cancer. Cancers. 2015;7(3):1499–1542.
   PubMed Web of Science ®Google Scholar
• Qin X, Yang L, Liu P, Yang L, Chen L, Hu L, Jiang M. Design, synthesis and biological evaluation of 2,3-dihydro-[1,4] dioxino [2,3-f] quinazoline derivatives as EGFR inhibitors. Bioorg Chem. 2021;110:104743.
   PubMed Web of Science ®Google Scholar
• Elmetwally SA, Saied KF, Eissa IH, Elkaeed EB. Design, synthesis and anticancer evaluation of thieno [2,3-d] pyrimidine derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers. Bioorg Chem. 2019;88:102944.
   PubMed Web of Science ®Google Scholar
• Marzaro G, Castagliuolo I, Schirato G, Palu’ G, Dalla Via M, Chilin A, Brun P. Substituted quinazolinones as kinase inhibitors endowed with anti-fibrotic properties. Eur J Med Chem. 2016;115:416–425.
   PubMed Web of Science ®Google Scholar
• Ewes WA, Elmorsy MA, El-Messery SM, Nasr MN. Synthesis, biological evaluation and molecular modeling study of [1,2,4]-triazolo [4,3-c] quinazolines: new class of EGFR-TK inhibitors. Bioorg Med Chem. 2020;28(7):115373.
   PubMed Web of Science ®Google Scholar
• Emam AM, Dahal A, Singh SS, Tosso RD, Ibrahim SM, El‐Sadek M, Jois SD, Enriz RD, Kothayer H. Quinazoline‐tethered hydrazone: a versatile scaffold toward dual anti‐TB and EGFR inhibition activities in NSCLC. Arch Pharm. 2021;354(12):2100281.
   Web of Science ®Google Scholar
• Aziz MW, Kamal AM, Mohamed KO, Elgendy AA. Design, synthesis and assessment of new series of quinazolinone derivatives as EGFR inhibitors along with their cytotoxic evaluation against MCF7 and A549 cancer cell lines. Bioorg Med Chem Lett. 2021;41:127987.
   PubMed Web of Science ®Google Scholar
• do Amaral DN, Lategahn J, Fokoue HH, da Silva EMB, Sant’Anna CMR, Rauh D, Barreiro EJ, Laufer S, Lima LM. A novel scaffold for EGFR inhibition: introducing n-(3-(3-phenylureido) quinoxalin-6-yl) acrylamide derivatives. Sci Rep. 2019;9(1):1–12.
   PubMedGoogle Scholar
• Jiang N, Bu Y, Wang Y, Nie M, Zhang D, Zhai X. Design, synthesis and structure-activity relationships of novel diaryl urea derivatives as potential EGFR inhibitors. Molecules. 2016;21(11):1572.
   PubMed Web of Science ®Google Scholar
• Sakr A, Rezq S, Ibrahim SM, Soliman E, Baraka MM, Romero DG, Kothayer H. Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: Anti-inflammatory, analgesic and anticancer activities. J Enzyme Inhib Med Chem. 2021;36(1):1810–1828.
   PubMed Web of Science ®Google Scholar
• Wang C, Li Y, Liu Z, Wang Z, Liu Z, Man S, Zhang Y, Bao K, Wu Y, Guan Q, et al. Design, synthesis and biological evaluation of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1 h-tetrazols as novel microtubule destabilizers. J Enzyme Inhib Med Chem. 2021;36(1):549–560.
   PubMed Web of Science ®Google Scholar
• Aboul-Enein MN, El-Azzouny AA, Attia MI, Maklad YA, Amin KM, Abdel-Rehim M, El-Behairy MF. Design and synthesis of novel stiripentol analogues as potential anticonvulsants. Eur J Med Chem. 2012;47(1):360–369.
   PubMedGoogle Scholar
• Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer. 2006;6(10):813–823.
   PubMed Web of Science ®Google Scholar
• RCSB protein data bank (pdb). Available from: http://www.rcsb.org.
   Google Scholar
• Molecular operating environment (MOE 2019.0102). Montreal: Chemical Computing Group Inc. Available from: http://www.chemcomp.com.2019.0102
   Google Scholar
• Lee SY, Kim HJ, Han JS. Anti-inflammatory effect of oyster shell extract in LPS-stimulated raw 264.7 cells. Prev Nutr Food Sci. 2013;18(1):23–29.
   PubMedGoogle Scholar
• Perkins DJ, Kniss DA. Blockade of nitric oxide formation down-regulates cyclooxygenase-2 and decreases PGE2 biosynthesis in macrophages. J Leukoc Biol. 1999;65(6):792–799.
   PubMed Web of Science ®Google Scholar
• Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longevity. 2017;2017:1–13.
   Web of Science ®Google Scholar
• Qi S, Feng Z, Li Q, Qi Z, Zhang Y. Myricitrin modulates NADPH oxidase-dependent ROS production to inhibit endotoxin-mediated inflammation by blocking the JAK/STAT1 and NOX2/P47(PHOX) pathways. Oxid Med Cell Longev. 2017;2017:9738745.
   PubMed Web of Science ®Google Scholar
• Chan A, Murin S. Up in smoke: the fallacy of the harmless hookah. Chest. 2011;139(4):737–738.
   PubMed Web of Science ®Google Scholar
• Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 2003;60(1):6–20.
   PubMed Web of Science ®Google Scholar
• Fujita M, Somasundaram V, Basudhar D, Cheng RYS, Ridnour LA, Higuchi H, Imadome K, No JH, Bharadwaj G, Wink DA. Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype. Redox Biol. 2019;22:101158.
   PubMed Web of Science ®Google Scholar
• Wang W, Xu R-L, He P, Chen R. Mar1 suppresses inflammatory response in LPS-induced raw 264.7 macrophages and human primary peripheral blood mononuclear cells via the SIRT1/PGC-1Α/PPAR-γ pathway. J Inflamm. 2021;18(1):8.
   Google Scholar
• Soromou LW, Zhang Z, Li R, Chen N, Guo W, Huo M, Guan S, Lu J, Deng X. Regulation of inflammatory cytokines in lipopolysaccharide-stimulated raw 264.7 murine macrophage by 7-o-methyl-naringenin. Molecules. 2012;17(3):3574–3585.
   PubMed Web of Science ®Google Scholar
• Selinsky BS, Gupta K, Sharkey CT, Loll PJ. Structural analysis of NSAID binding by prostaglandin H2 synthase: Time-dependent and time-independent inhibitors elicit identical enzyme conformations. Biochemistry. 2001;40(17):5172–5180.
   PubMed Web of Science ®Google Scholar
• Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996;384(6610):644–648.
   PubMed Web of Science ®Google Scholar
• Kobe MJ, Neau DB, Mitchell CE, Bartlett SG, Newcomer ME. The structure of human 15-lipoxygenase-2 with a substrate mimic. J Biol Chem. 2014;289(12):8562–8569.
   PubMed Web of Science ®Google Scholar
• Stamos J, Sliwkowski MX, Eigenbrot C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem. 2002;277(48):46265–46272.
   PubMed Web of Science ®Google Scholar
• Hanan EJ, Baumgardner M, Bryan MC, Chen Y, Eigenbrot C, Fan P, Gu X-H, La H, Malek S, Purkey HE, et al. 4-Aminoindazolyl-dihydrofuro [3,4-d] pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase. Bioorg Med Chem Lett. 2016;26(2):534–539.
   PubMed Web of Science ®Google Scholar
• Heald R, Bowman KK, Bryan MC, Burdick D, Chan B, Chan E, Chen Y, Clausen S, Dominguez-Fernandez B, Eigenbrot C, et al. Noncovalent mutant selective epidermal growth factor receptor inhibitors: a lead optimization case study. J Med Chem. 2015;58(22):8877–8895.
   PubMed Web of Science ®Google Scholar
• Hanan EJ, Eigenbrot C, Bryan MC, Burdick DJ, Chan BK, Chen Y, Dotson J, Heald RA, Jackson PS, La H, et al. Discovery of selective and noncovalent diaminopyrimidine-based inhibitors of epidermal growth factor receptor containing the T790M resistance mutation. J Med Chem. 2014;57(23):10176–10191.
   PubMed Web of Science ®Google Scholar