New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAF^V600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study

References

• Othman EM, Fayed EA, Husseiny EM, et al. Apoptosis induction, PARP-1 inhibition, and cell cycle analysis of leukemia cancer cells treated with novel synthetic 1,2,3-triazole-chalcone conjugates. Bioorg Chem. 2022;123:1–15.
   Web of Science ®Google Scholar
• Khalifa M, Allahloubi N, Salem S, Mahmoud M, Zekri A. Correlation between strength of estrogen receptor positivity and outcome of adjuvant tamoxifen therapy in breast cancer patients. Zagazig Univ Med J. 2020;0(0):0–0.
   Google Scholar
• Karn A, Jha AK, Shrestha S, Acharya B, Poudel S, Bhandari RB. Tamoxifen for breast cancer. J Nepal Med Assoc. 2010;49(177):62–67.
   PubMedGoogle Scholar
• Keely NO, Carr M, Yassin B, Ana G, Lloyd DG, Zisterer D, Meegan MJ. Design, synthesis and biochemical evaluation of novel selective estrogen receptor ligand conjugates incorporating an endoxifen-combretastatin hybrid scaffold. Biomedicines. 2016;4(3):15.
   PubMedGoogle Scholar
• Ghosh D, Griswold J, Erman M, Pangborn W. Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature. 2009;457(7226):219–223.
   PubMed Web of Science ®Google Scholar
• Leechaisit R, Pingaew R, Prachayasittikul V, et al. Synthesis, molecular docking, and QSAR study of bis-sulfonamide derivatives as potential aromatase inhibitors. Bioorganic Med Chem. 2019;27:1–10.
   PubMedGoogle Scholar
• Fantacuzzi M, De Filippis B, Gallorini M, et al. Synthesis, biological evaluation, and docking study of indole aryl sulfonamides as aromatase inhibitors. Eur J Med Chem. 2020;185:1–14.
   Web of Science ®Google Scholar
• Lekgau K, Raphoko LA, Lebepe CM, et al. Design and synthesis of 6-amino-quinoxaline-alkynyl as potential aromatase (CYP19A1) inhibitors. J Mol Struct. 2022;1255:1–16.
   Web of Science ®Google Scholar
• Geisler J. Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole- of clinical importance. Br J Cancer. 2011;104(7):1059–1066.
   PubMed Web of Science ®Google Scholar
• Giampietro L, Gallorini M, Gambacorta N, Ammazzalorso A, De Filippis B, Della Valle A, Fantacuzzi M, Maccallini C, Mollica A, Cataldi A, et al. Synthesis, structure-activity relationships and molecular docking studies of phenyldiazenyl sulfonamides as aromatase inhibitors. Eur J Med Chem. 2021;224:113737.
   PubMed Web of Science ®Google Scholar
• Çetiner G, Acar U, Celik I, et al. New imidazole derivatives as aromatase inhibitor : Design, synthesis, biological activity, molecular docking, and computational ADME-Tox studies. 2023;1278.
   Google Scholar
• Zhou S, Liu Y, Jin L, Guo P, Liu Q, Shan J, Luo X, He H, Ma W, Zhang TCun, et al. Estrogen enhances the cytotoxicity of PARP inhibitors on breast cancer cells through stimulating nitric oxide production. J Steroid Biochem Mol Biol. 2021;209:105853.
   PubMed Web of Science ®Google Scholar
• Sund M, Garcia-Argibay M, Garmo H, Ahlgren J, Wennstig A-K, Fredriksson I, Lindman H, Valachis A. Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study. Breast. 2021;59:157–164.
   PubMed Web of Science ®Google Scholar
• Karpov OA, Fearnley GW, Smith GA, et al. Receptor tyrosine kinase structure and function in health and disease. AIMS Biophys. 2015;2:476–502.
   Google Scholar
• Celik I, Ayhan‐Kılcıgil G, Karayel A, Guven B, Onay‐Besikci A. Synthesis, molecular docking, in silico ADME, and EGFR kinase inhibitor activity studies of some new benzimidazole derivatives bearing thiosemicarbazide, triazole, and thiadiazole. Journal of Heterocyclic Chem. 2022;59(2):371–387.
   Web of Science ®Google Scholar
• Purba ER, Saita E-I, Maruyama IN. Mechanisms of activation of receptor tyrosine kinases: Monomers or dimers. Cells. 2014;6(2):304–330.
   Google Scholar
• Hubbard SR, Mohammadi M, Schlessinger J. Autoregulatory mechanisms in protein-tyrosine kinases. J Biol Chem. 1998;273(20):11987–11990.
   PubMed Web of Science ®Google Scholar
• Butti R, Das S, Gunasekaran VP, Yadav AS, Kumar D, Kundu GC. Receptor tyrosine kinases (RTKs) in breast cancer: Signaling, therapeutic implications and challenges. Mol Cancer. 2018;17(1):34.
   PubMedGoogle Scholar
• Naishima NL, Faizan S, Raju RM. Design, synthesis, analysis, evaluation of cytotoxicity against MCF-7 breast cancer cells, 3D QSAR studies and EGFR, HER2 inhibition studies on novel Biginelli 1,4-Dihydropyrimidines. J Mol Struct. 2023;1277:1–23.
   Web of Science ®Google Scholar
• Mitri Z, Constantine T, O'Regan R. The HER2 receptor in breast cancer: pathophysiology, clinical use, and new advances in therapy. Chemother Res Pract. 2012;2012:743193–743197.
   PubMedGoogle Scholar
• Mohmmed EA, Ramadan SS, EL-Saiid AS, Shousha WG. Frequency and clinical features of over-expressed her2 in Egyptian breast cancer women patients. Egypt J Hosp Med. 2021;85(1):3431–3435.
   Google Scholar
• Martínez-Sáez O, Prat A. Current and future management of HER2-Positive metastatic breast cancer. JCO Oncol Pract. 2021;17(10):594–604.
   PubMedGoogle Scholar
• Notarangelo T, Sisinni L, Condelli V, Landriscina M. Dual EGFR and BRAF blockade overcomes resistance to vemurafenib in BRAF mutated thyroid carcinoma cells. Cancer Cell Int. 2017;17(1):86.
   PubMedGoogle Scholar
• Tong CWS, Wu M, Cho WCS, To KKW. Recent advances in the treatment of breast cancer. Front Oncol. 2018;8:227.
   PubMed Web of Science ®Google Scholar
• Pircher M, Winder T, Trojan A. Response to vemurafenib in metastatic triple-negative breast cancer harbouring a BRAF V600E mutation: a case report and electronically captured patient-reported outcome. Case Rep Oncol. 2021;14(1):616–621.
   PubMed Web of Science ®Google Scholar
• Abdel-Maksoud MS, El-Gamal MI, Gamal El-Din MM, Oh CH. Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety. J Enzyme Inhib Med Chem. 2019;34(1):97–109.
   PubMed Web of Science ®Google Scholar
• Halim PA, Sharkawi SMZ, Labib MB. Novel pyrazole-based COX-2 inhibitors as potential anticancer agents: design, synthesis, cytotoxic effect against resistant cancer cells, cell cycle arrest, apoptosis induction and dual EGFR/Topo-1 inhibition. Bioorg Chem. 2022;131:106273.
   PubMed Web of Science ®Google Scholar
• Al-Wahaibi LH, Mohammed AF, Abdelrahman MH, Trembleau L, Youssif BGM. Citation and bgmy, trembleau. design, synthesis, and antiproliferative activity of new 5-chloro-indole-2-carboxylate and Pyrrolo[3,4-b]indol-3-one derivatives as potent inhibitors of EGFRT790M/BRAFV600E pathways lamya. Molecules. 2023;28(3):1269.
   PubMed Web of Science ®Google Scholar
• Giordano S, Petrelli A. From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr Med Chem. 2008;15(5):422–432.
   PubMed Web of Science ®Google Scholar
• Katopodis P, Chudasama D, Wander G, Sales L, Kumar J, Pandhal M, Anikin V, Chatterjee J, Hall M, Karteris E. Kinase inhibitors and ovarian cancer. Cancers (Basel). 2019;11(9):1357.
   PubMed Web of Science ®Google Scholar
• Vultur A, Villanueva J, Herlyn MM. BRAF inhibitor unveils its potential against advanced melanoma. Cancer Cell. 2010;18(4):301–302.
   PubMed Web of Science ®Google Scholar
• Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–954.,.
   PubMed Web of Science ®Google Scholar
• Ho C-C, Liao W-Y, Lin C-A, Shih J-Y, Yu C-J, Yang JC-H. Acquired BRAF V600E mutation as resistant mechanism after treatment with osimertinib. J Thorac Oncol. 2017;12(3):567–572.
   PubMed Web of Science ®Google Scholar
• Zhang J, Li Y, Chen S, Zhang L, Wang J, Yang Y, Zhang S, Pan Y, Wang Y, Yang Y. Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb folium eriobotryae. Int J Mol Sci. 2015;16(2):2913–2941.
   PubMed Web of Science ®Google Scholar
• Abdellatif KRA, Eman KAÁ, Wael AA, Fadaly  , Kamel GM. Synthesis, cyclooxygenase inhibition, anti- inflammatory evaluation and ulcerogenic chemistry. Med Chem Res. 2015;7
   Google Scholar
• Stankov SV. Definition of inflammation, causes of inflammation and possible anti-inflammatory strategies. Open Inflamm J. 2012;5:1–9.
   Google Scholar
• Abdellatif KRA, Elsaady MT, Amin NH. Design, synthesis and biological evaluation of some novel indole derivatives as selective COX-2 inhibitors. J Appl Pharm Sci. 2017;7:69–77.
   Google Scholar
• Dubios RN, Abrasmin SB, Crafford L, et al. Cyclooxygenase in biology and disease. Faseb J. 1998;12:1063–1073.
   PubMedGoogle Scholar
• Abdellatif KRA, Abdelall EKA, Labib MB, Fadaly WAA, Zidan TH. Design, synthesis of celecoxib-tolmetin drug hybrids as selective and potent COX-2 inhibitors. Bioorg Chem. 2019;90:103029.
   PubMed Web of Science ®Google Scholar
• Abdellatif KRA, Fadaly WAA. Design, synthesis, cyclooxygenase inhibition and biological evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing amino/methanesulfonyl pharmacophore. Bioorg Chem. 2017;70:57–66.
   PubMed Web of Science ®Google Scholar
• Abdellatif KRA, Abdelgawad MA, Labib MB, Zidan TH. Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of novel triarylpyrazoline derivatives as selective COX-2 inhibitors. Bioorg Med Chem Lett. 2015;25(24):5787–5791.
   PubMed Web of Science ®Google Scholar
• Grosser T, Fries S, Fitzgerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition : therapeutic challenges and opportunities. J Clin Invest. 2006;116(1):4–15.
   PubMed Web of Science ®Google Scholar
• Khaled RA, Abdellatif Eman KA, Abdelall MA, Abdelgawad MMA, Hany AO. Design and synthesis of certain novel arylidene thiazolidinone derivatives as anticancer agents. Derpharmachemica. 2015;7:149–161.
   Google Scholar
• Gupta V, Yadav S. Cyclooxygenase-2: pathway form anti-inflammatory to anti- cancer drugs. Int J Pharm Life Sci. 2011;2:571–582.
   Google Scholar
• Singh B, Lucci A. Role of cyclooxygenase-2 in breast cancer. J Surg Res. 2002;108(1):173–179.
   PubMed Web of Science ®Google Scholar
• Koki AT, Masferrer JL. Celecoxib: a specific COX-2 inhibitor with anticancer properties. Cancer Control. 2002;9(2 Suppl):28–35.
   PubMedGoogle Scholar
• Harris RE. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology. 2009;17(2):55–67.
   PubMedGoogle Scholar
• Stolfi C, De Simone V, Pallone F, Monteleone G. Mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDs) and mesalazine in the chemoprevention of colorectal cancer. Int J Mol Sci. 2013;14(9):17972–17985.
   PubMed Web of Science ®Google Scholar
• Mittal A, Dixit S, Rana S. Anticancer effects of chemotherapy and nature products. J Med Discov. 2017;2:1–9.
   Google Scholar
• Denkova AG, Liu H, Men Y, et al. Enhanced cancer therapy by combining radiation and chemical effects mediated by nanocarriers. Adv Ther. 2020;3:1–17.
   Google Scholar
• Fu S-L, Wu Y-L, Zhang Y-P, Qiao M-M, Chen Y. Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer. World J Gastroenterol. 2004;10(13):1971–1974.
   PubMed Web of Science ®Google Scholar
• Abdelhaleem EF, Kassab AE, El-Nassan HB, Khalil OM. Design, synthesis, and biological evaluation of new celecoxib analogs as apoptosis inducers and cyclooxygenase-2 inhibitors. Arch Pharm (Weinheim)). 2022;355(11):e2200190.
   PubMed Web of Science ®Google Scholar
• Abuo-Rahma GE-DAA, Abdel-Aziz M, Beshr EAM, Ali TFS. 1,2,4-Triazole/oxime hybrids as new strategy for nitric oxide donors: synthesis, anti-inflammatory, ulceroginicity and antiproliferative activities. Eur J Med Chem. 2014;71:185–198.
   PubMed Web of Science ®Google Scholar
• Abuo-Rahma GE-DAA, Abdel-Aziz M, Mourad MAE, Farag HH. Synthesis, anti-inflammatory activity and ulcerogenic liability of novel nitric oxide donating/chalcone hybrids. Bioorg Med Chem. 2012;20(1):195–206.
   PubMed Web of Science ®Google Scholar
• Zhang X, Ding J, Feng L, et al. Development of novel nitric oxide-releasing quinolinedione/furoxan hybrids as NQO1 inhibitors for intervention of drug-resistant hepatocellular cancer. Bioorg Chem. 2022;129:1–11.
   Web of Science ®Google Scholar
• Shafran Y, Zurgil N, Ravid-Hermesh O, Sobolev M, Afrimzon E, Hakuk Y, Shainberg A, Deutsch M. Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis. Oncotarget. 2017; 8(65):108890–108911.
   PubMedGoogle Scholar
• Eissa AG, Barrow D, Gee J, Powell LE, Foster PA, Simons C. 4th Generation nonsteroidal aromatase inhibitors: an iterative SAR-guided design, synthesis, and biological evaluation towards picomolar dual binding inhibitors. Eur J Med Chem. 2022;240:114569.
   PubMed Web of Science ®Google Scholar
• Fadaly WAA, Elshaier YAMM, Hassanein EHM, et al. New 1,2,4-triazole/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release. Bioorg Chem. 2020;98:1–20.
   Web of Science ®Google Scholar
• Fadaly WAA, Elshaier YAMM, Nemr MTM, et al. Bioorganic chemistry design, synthesis, modeling studies and biological evaluation of pyrazole derivatives linked to oxime and nitrate moieties as nitric oxide donor selective COX-2 and aromatase inhibitors with dual anti-inflammatory and anti-neoplasti. Bioorg Chem. 2023;134:106428.
   PubMed Web of Science ®Google Scholar
• Duan Y-C, Ma Y-C, Zhang E, Shi X-J, Wang M-M, Ye X-W, Liu H-M. Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents. Eur J Med Chem. 2013;62:11–19.
   PubMed Web of Science ®Google Scholar
• Becerril JLM, Benítez JGS, Juárez JJT, Bañales JMG, Zerón HM, Navarro MDH. Evaluation of the effect of 1,3-Bis(4-Phenyl)-1H-1,2,3-Triazolyl-2-propanolol on gene expression levels of JAK2–STAT3, NF-κB, and SOCS3 in cells cultured from biopsies of mammary lesions. Biochem Genet. 2015;53(11-12):291–300.
   PubMed Web of Science ®Google Scholar
• Hou Y-P, Sun J, Pang Z-H, Lv P-C, Li D-D, Yan L, Zhang H-J, Zheng EX, Zhao J, Zhu H-L, et al. Synthesis and antitumor activity of 1,2,4-triazoles having 1,4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors. Bioorg Med Chem. 2011;19(20):5948–5954.
   PubMed Web of Science ®Google Scholar
• Kaoud TS, Mohassab AM, Hassan HA, et al. NO-releasing STAT3 inhibitors suppress BRAF-mutant melanoma growth. Eur J Med Chem. 2020;186:1–65.
   Web of Science ®Google Scholar
• AboulWafa OM, Daabees HMG, El-Said AH. Benzoxazole-appended piperidine derivatives as novel anticancer candidates against breast cancer. Bioorg Chem. 2023;134:106437.
   PubMed Web of Science ®Google Scholar
• Kouznetsov VV, Gómez-Barrio A. Recent developments in the design and synthesis of hybrid molecules basedon aminoquinoline ring and their antiplasmodial evaluation. Eur J Med Chem. 2009;44(8):3091–3113.
   PubMed Web of Science ®Google Scholar
• Bekheit MS, Mohamed HA, Abdel-Wahab BF, Fouad MA. Design and synthesis of new 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety as selective COX-2 inhibitors. Med Chem Res. 2021;30(5):1125–1138.
   Web of Science ®Google Scholar
• Abdelrazek FM, Hassaneen HM, Nassar EM. Phenacyl bromides revisited: facile synthesis of some new pyrazoles, pyridazines, and their fused derivatives. J Heterocycl Chem. 2011;46:475–481.
   Google Scholar
• Akbarzadeh A, Soleymani R, Taheri M, Rajabzadeh H, Daryani M. Synthesis and studies of potential antifungal and antibacterial agents new aryl thiazolyl mercury (II) derivatives compounds. J Chem. 2013;2013:1–6.
   Web of Science ®Google Scholar
• Hussein AHM, Khames AA, El-Adasy A-BA, Atalla AA, Abdel-Rady M, Hassan MIA, Nemr MTM, Elshaier YAAM. Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors. RSC Adv. 2020;10(50):29723–29736.
   PubMed Web of Science ®Google Scholar
• Omar HA, Arafa E-SA, Salama SA, Arab HH, Wu C-H, Weng J-R. OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting Akt-NF-κB and MAPK signaling pathways. Toxicol Appl Pharmacol. 2013;272(3):616–624.
   PubMed Web of Science ®Google Scholar
• Nemr MTM, AboulMagd AM, Hassan HM, Hamed AA, Hamed MIA, Elsaadi MT. Design, synthesis and mechanistic study of new benzenesulfonamide derivatives as anticancer and antimicrobial agentsviacarbonic anhydrase IX inhibition. RSC Adv. 2021;11(42):26241–26257.
   PubMed Web of Science ®Google Scholar
• Zaher AF, Abuel-Maaty SM, El-Nassan HB, Amer SAS, Abdelghany TM. Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives. J Enzyme Inhib Med Chem. 2016;31(suppl 4):145–153.
   PubMedGoogle Scholar
• Ibrahim TS, Hawwas MM, Malebari AM, Taher ES, Omar AM, Neamatallah T, Abdel-Samii ZK, Safo MK, Elshaier YAMM. Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect. J Enzyme Inhib Med Chem. 2021;36(1):802–818.
   PubMed Web of Science ®Google Scholar
• Shawky AM, Ibrahim NA, Abdalla AN, Abourehab MAS, Gouda AM. Novel pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety: design, synthesis, molecular docking, and biological evaluation as potential multi-target cytotoxic agents. J Enz Inhib. 2021;36(1):1312–1332.
   Google Scholar
• Nakamura JL. The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications. Expert Opin Ther Targets. 2007;11(4):463–472.
   PubMed Web of Science ®Google Scholar
• Obaid NM, Bedard K, Huang WY. Strategies for overcoming resistance in tumours harboring BRAF mutations. Int J Mol Sci. 2017;18(3):585.
   PubMed Web of Science ®Google Scholar
• Wink DA, Ridnour LA, Hussain SP, Harris CC. The reemergence of nitric oxide and cancer. Nitric Oxide. 2008;19(2):65–67.
   PubMed Web of Science ®Google Scholar
• Abdellatif KRA, Belal A, Omar HA. Design, synthesis and biological evaluation of novel triaryl (Z)-olefins as tamoxifen analogues. Bioorg Med Chem Lett. 2013;23(17):4960–4963.
   PubMed Web of Science ®Google Scholar
• Çetiner G, Acar Çevik U, Celik I. New imidazole derivatives as aromatase inhibitor: design, synthesis, biological activity, molecular docking, and computational ADME-Tox studies. J Mol Struct. 2023;1278:1–9.
   Web of Science ®Google Scholar
• Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JRB, Liao S, Pawlitz JL, Kurumbail RG, Maziasz T, Talley JJ, et al. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life. Bioorg Med Chem Lett. 2010;20(23):7159–7163.
   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