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Innovative piperidone derivatives: a new horizon in Potent anticancer therapeutics
Corresponding Author(s) : K. Anuja
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 12 No. 3 (2024): 2024 Volume -12 - Issue 3
Abstract
Recent advancements in the synthesis and evaluation of piperidone derivatives have unveiled their remarkable potential as potent anticancer agents. This review highlights the innovative approaches and significant findings in the development of novel piperidone-based compounds, showcasing their efficacy against various cancer cell lines. Among the noteworthy compounds, dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs) have demonstrated selective cytotoxicity with minimal impact on normal cells. Further, modifications involving N-benzoylation, N-benzenesulfonylation and N-acryloylation have enhanced the cytotoxic profiles of these derivatives, revealing significant activity against carcinoma, leukaemia, and colon cancer cell lines. QSAR studies and computer docking simulations have provided insights into the structural requirements for optimizing anticancer potency and selectivity. In vivo studies confirm the therapeutic potential of key compounds, demonstrating tumour growth inhibition with minimal toxicity. This comprehensive review underscores the transformative potential of piperidone derivatives, paving the way for their development as next-generation anticancer therapeutics.
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- Siddiqui IA, Sanna V, Ahmad N, Sechi M, Mukhtar H. Resveratrol nano formulation for cancer prevention and therapy. Annals of the New York Academy of Sciences. 2015 Aug;1348(1):20-31.
- De Silva F, Alcorn J. A tale of two cancers: A current concise overview of breast and prostate cancer. Cancers. 2022 Jun 15;14(12):2954.
- S.A. Norton, M.N. Wittink, P.R. Duberstein, H.G. Prigerson, S. Stanek, R. M. Epstein, Family caregiver descriptions of stopping chemotherapy and end-of life transitions, Support, Care Cancer. 2019; 27: 669–675.
- R. Hassan, B. Morrow, A. Thomas, T. Walsh, M.K. Lee, S. Gulsuner, J. Khan, Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy, Proc. Natl. Acad. Sci. Unit. States Am. 2019; 116: 9008–9013.
- S. Giri, J.C. Bose, A. Chandrasekar, B.K. Tiwary, P. Gajalakshmi, S. Chatterjee, Increased plasma nitrite and von Willebrand factor indicates early diagnosis of vascular diseases in chemotherapy treated cancer patients, Cardiovasc. Toxicol. 2019; 19:36–47
- E.M. Gibson, S. Nagaraja, A. Ocampo, L.T. Tam, L.S. Wood, P.N. Pallegar, P. J. Woo, Methotrexate chemotherapy induces persistent tri-glial dysregulation that underlies chemotherapy-related cognitive impairment, Cell. 2019; 176: 43–55.
- Safaei M, Shishehbore MR. A review on analytical methods with special reference to electroanalytical methods for the determination of some anticancer drugs in pharmaceutical and biological samples. Talanta. 2021 Jul 1; 229:122247.
- Dimmock JR, Padmanilayam MP, Puthucode RN, Nazarali AJ, Motaganahalli NL, Zello GA, Quail JW, Oloo EO, Kraatz HB, Prisciak JS, Allen TM. A conformational and structure− activity relationship study of cytotoxic 3, 5-bis (arylidene)-4-piperidones and related N-acryloyl analogues. Journal of Medicinal Chemistry. 2001 Feb 15;44(4):586-93.
- Dimmock JR, Elias DW, Beazely MA, Kandepu NM. Bioactivities of chalcones. Curr Med Chem. 1999 Dec;6(12):1125-49. PMID: 10519918.
- Addala E, Rafiei H, Das S, Bandy B, et al. 3,5-Bis (3-dimethylaminomethyl-4- hydroxybenzylidene)-4-piperidone and related compounds induce glutathione oxidation and mitochondria-mediated cell death in HCT-116 cells. Bioorg Med Chem Lett. 2017; 27:3669- 3673.
- Karki SS, Das U, Umemura N, Sakagami H, et al. 3,5-Bis(3-alkylaminomethyl)-4- hydroxybenzylidene)-4-piperidones: A novel class of potent tumour-selective cytotoxins. J Med Chem. 2016; 59:763-769.
- Edraki N, Das U, Hemateenejad B, Dimmock JR, et al. Comparative QSAR analysis of 3,5- bis(arylidene)-4-piperidone derivatives: the development of predictive cytotoxicity models. Iran J Pharm Res. 2016; 15:425-437.
- Li N, Xin WY, Yao BR, Wang CH, Cong W, Zhao F, Li HJ, Hou Y, Meng QG, Hou GG. Novel dissymmetric 3, 5-bis (arylidene)-4-piperidones as potential antitumor agents with biological evaluation in vitro and in vivo. European Journal of Medicinal Chemistry. 2018 Mar 10; 147:21-33.
- Sun J, Zhang S, Yu C, Hou G, Zhang X, Li K, Zhao F. Design, Synthesis and Bioevaluation of Novel N‐Substituted‐3, 5‐Bis (Arylidene)‐4‐piperidone Derivatives as Cytotoxic and Antitumor Agents with Fluorescent Properties. Chemical Biology & Drug Design. 2014 Apr;83(4):392-400.
- Jadhav RL, Magdum CS, Patil MV. Synthesis and anticancer evaluation of furfurylidene 4‐piperidone analogs. Archiv der Pharmazie. 2014 Jun;347(6):407-14.
- Kálai T, Kuppusamy ML, Balog M, Selvendiran K, Rivera BK, Kuppusamy P, Hideg K. Synthesis of N-substituted 3, 5-bis (arylidene)-4-piperidones with high antitumor and antioxidant activity. Journal of medicinal chemistry. 2011 Aug 11;54(15):5414-21.
- Das U, Alcorn J, Shrivastav A, Sharma RK, De Clercq E, Balzarini J, Dimmock JR. Design, synthesis and cytotoxic properties of novel 1-[4-(2-alkylaminoethoxy) phenylcarbonyl]-3, 5-bis (arylidene)-4-piperidones and related compounds. European journal of medicinal chemistry. 2007 Jan 1;42(1):71-80.
- Das S, Das U, Michel D, Gorecki DK, Dimmock JR. Novel 3, 5-bis (arylidene)-4-piperidone dimers: Potent cytotoxins against colon cancer cells. European journal of medicinal chemistry. 2013 Jun 1; 64:321-8.
- Chhikara A, Roayapalley PK, Sakagami H, Amano S, Satoh K, Uesawa Y, Das U, Das S, Borrego EA, Guerena CD, Hernandez CR. Novel Unsymmetric 3, 5-Bis (benzylidene)-4-piperidones That Display Tumour-Selective Toxicity. Molecules. 2022 Oct 9;27(19):6718.
- Das S, Roayapalley PK, Sakagami H, Umemura N, Gorecki DK, Hossain M, Kawase M, Das U, Dimmock JR. Dimeric 3, 5-Bis (benzylidene)-4-piperidones: Tumour-Selective Cytotoxicity and Structure-Activity Relationships. Medicines. 2024 Jan 11;11(1):3.
- Nunes LM, Hossain M, Varela-Ramirez A, Das U, Ayala-Marin YM, Dimmock JR, Aguilera RJ. A novel class of piperidones exhibit potent, selective and pro-apoptotic anti-leukaemia properties. Oncology Letters. 2016 Jun;11(6):3842-8.
- Roayapalley PK, Dimmock JR, Contreras L, Balderrama KS, Aguilera RJ, Sakagami H, Amano S, Sharma RK, Das U. Design, synthesis and tumour-selective toxicity of novel 1-[3-{3, 5-Bis (benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes and related quaternary ammonium salts. Molecules. 2021 Nov 25;26(23):7132.
References
Siddiqui IA, Sanna V, Ahmad N, Sechi M, Mukhtar H. Resveratrol nano formulation for cancer prevention and therapy. Annals of the New York Academy of Sciences. 2015 Aug;1348(1):20-31.
De Silva F, Alcorn J. A tale of two cancers: A current concise overview of breast and prostate cancer. Cancers. 2022 Jun 15;14(12):2954.
S.A. Norton, M.N. Wittink, P.R. Duberstein, H.G. Prigerson, S. Stanek, R. M. Epstein, Family caregiver descriptions of stopping chemotherapy and end-of life transitions, Support, Care Cancer. 2019; 27: 669–675.
R. Hassan, B. Morrow, A. Thomas, T. Walsh, M.K. Lee, S. Gulsuner, J. Khan, Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy, Proc. Natl. Acad. Sci. Unit. States Am. 2019; 116: 9008–9013.
S. Giri, J.C. Bose, A. Chandrasekar, B.K. Tiwary, P. Gajalakshmi, S. Chatterjee, Increased plasma nitrite and von Willebrand factor indicates early diagnosis of vascular diseases in chemotherapy treated cancer patients, Cardiovasc. Toxicol. 2019; 19:36–47
E.M. Gibson, S. Nagaraja, A. Ocampo, L.T. Tam, L.S. Wood, P.N. Pallegar, P. J. Woo, Methotrexate chemotherapy induces persistent tri-glial dysregulation that underlies chemotherapy-related cognitive impairment, Cell. 2019; 176: 43–55.
Safaei M, Shishehbore MR. A review on analytical methods with special reference to electroanalytical methods for the determination of some anticancer drugs in pharmaceutical and biological samples. Talanta. 2021 Jul 1; 229:122247.
Dimmock JR, Padmanilayam MP, Puthucode RN, Nazarali AJ, Motaganahalli NL, Zello GA, Quail JW, Oloo EO, Kraatz HB, Prisciak JS, Allen TM. A conformational and structure− activity relationship study of cytotoxic 3, 5-bis (arylidene)-4-piperidones and related N-acryloyl analogues. Journal of Medicinal Chemistry. 2001 Feb 15;44(4):586-93.
Dimmock JR, Elias DW, Beazely MA, Kandepu NM. Bioactivities of chalcones. Curr Med Chem. 1999 Dec;6(12):1125-49. PMID: 10519918.
Addala E, Rafiei H, Das S, Bandy B, et al. 3,5-Bis (3-dimethylaminomethyl-4- hydroxybenzylidene)-4-piperidone and related compounds induce glutathione oxidation and mitochondria-mediated cell death in HCT-116 cells. Bioorg Med Chem Lett. 2017; 27:3669- 3673.
Karki SS, Das U, Umemura N, Sakagami H, et al. 3,5-Bis(3-alkylaminomethyl)-4- hydroxybenzylidene)-4-piperidones: A novel class of potent tumour-selective cytotoxins. J Med Chem. 2016; 59:763-769.
Edraki N, Das U, Hemateenejad B, Dimmock JR, et al. Comparative QSAR analysis of 3,5- bis(arylidene)-4-piperidone derivatives: the development of predictive cytotoxicity models. Iran J Pharm Res. 2016; 15:425-437.
Li N, Xin WY, Yao BR, Wang CH, Cong W, Zhao F, Li HJ, Hou Y, Meng QG, Hou GG. Novel dissymmetric 3, 5-bis (arylidene)-4-piperidones as potential antitumor agents with biological evaluation in vitro and in vivo. European Journal of Medicinal Chemistry. 2018 Mar 10; 147:21-33.
Sun J, Zhang S, Yu C, Hou G, Zhang X, Li K, Zhao F. Design, Synthesis and Bioevaluation of Novel N‐Substituted‐3, 5‐Bis (Arylidene)‐4‐piperidone Derivatives as Cytotoxic and Antitumor Agents with Fluorescent Properties. Chemical Biology & Drug Design. 2014 Apr;83(4):392-400.
Jadhav RL, Magdum CS, Patil MV. Synthesis and anticancer evaluation of furfurylidene 4‐piperidone analogs. Archiv der Pharmazie. 2014 Jun;347(6):407-14.
Kálai T, Kuppusamy ML, Balog M, Selvendiran K, Rivera BK, Kuppusamy P, Hideg K. Synthesis of N-substituted 3, 5-bis (arylidene)-4-piperidones with high antitumor and antioxidant activity. Journal of medicinal chemistry. 2011 Aug 11;54(15):5414-21.
Das U, Alcorn J, Shrivastav A, Sharma RK, De Clercq E, Balzarini J, Dimmock JR. Design, synthesis and cytotoxic properties of novel 1-[4-(2-alkylaminoethoxy) phenylcarbonyl]-3, 5-bis (arylidene)-4-piperidones and related compounds. European journal of medicinal chemistry. 2007 Jan 1;42(1):71-80.
Das S, Das U, Michel D, Gorecki DK, Dimmock JR. Novel 3, 5-bis (arylidene)-4-piperidone dimers: Potent cytotoxins against colon cancer cells. European journal of medicinal chemistry. 2013 Jun 1; 64:321-8.
Chhikara A, Roayapalley PK, Sakagami H, Amano S, Satoh K, Uesawa Y, Das U, Das S, Borrego EA, Guerena CD, Hernandez CR. Novel Unsymmetric 3, 5-Bis (benzylidene)-4-piperidones That Display Tumour-Selective Toxicity. Molecules. 2022 Oct 9;27(19):6718.
Das S, Roayapalley PK, Sakagami H, Umemura N, Gorecki DK, Hossain M, Kawase M, Das U, Dimmock JR. Dimeric 3, 5-Bis (benzylidene)-4-piperidones: Tumour-Selective Cytotoxicity and Structure-Activity Relationships. Medicines. 2024 Jan 11;11(1):3.
Nunes LM, Hossain M, Varela-Ramirez A, Das U, Ayala-Marin YM, Dimmock JR, Aguilera RJ. A novel class of piperidones exhibit potent, selective and pro-apoptotic anti-leukaemia properties. Oncology Letters. 2016 Jun;11(6):3842-8.
Roayapalley PK, Dimmock JR, Contreras L, Balderrama KS, Aguilera RJ, Sakagami H, Amano S, Sharma RK, Das U. Design, synthesis and tumour-selective toxicity of novel 1-[3-{3, 5-Bis (benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes and related quaternary ammonium salts. Molecules. 2021 Nov 25;26(23):7132.