Skip to main content

Advertisement

SpringerLink
Log in

A review on pharmacophoric designs of antiproliferative agents

  • Review Article
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Past few decades have witnessed the dawn of new diseases in which cancer is a major problem and the race ensued to eradicate cancer by charting out various effective therapeutic regimens. Circumventing resistance issues and combating the toxicity and selectivity problems are matter-of-concern in cancer treatment. Persistent failure to ensure complete remission and eradication of cancer instigated the researchers to exploit the strategies of combining pharmacophores as targeted therapeutic agents. Momentous improvement in the pharmacokinetic as well as pharmacodynamic profile resulting in the enhancement of bioavailability was seen with the introduction of these pharmacophores. The scope of molecular hybridization can be clearly exemplified through the US-FDA approved estramustine and others such as CUDC-101, CBLC-137, PLX3397, E-3810, and CUDC-907 that are currently in different phases of clinical trials. This review seeks to highlight and discuss anti-proliferative activity of some important hybrid, dual, and multi-targeted pharmacophores reported to date along with their designs, structure activity relationships, scope, and limitations. Further, an emphasis has been made to summarize US-FDA approved as well as drugs currently undergoing clinical trials of anticancer drug development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19
Fig. 20
Fig. 21
Fig. 22
Fig. 23
Fig. 24
Fig. 25

Similar content being viewed by others

References and notes

  • Abogye EO, Kaliszczak MA (2012) Combination treatment comprising a HDAC6 inhibitor and an AKT Inhibitor. WO Patent 2,012,175,973

  • Ai T, Cui H, Chen L (2012) Multi-targeted histone deacetylase inhibitors in cancer therapy. Curr Med Chem 19:475–487

    CAS  PubMed  Google Scholar 

  • Ali MB (2014) Physiological mechanisms and adaptation strategies in plants under changing environment. Springer, London

    Google Scholar 

  • Amaral C, Varela C, Borges M, da Silva ET, Roleira FM, Correia-da-Silva G, Teixeira N (2013) Steroidal aromatase inhibitors inhibit growth of hormone-dependent breast cancer cells by inducing cell cycle arrest and apoptosis. Apoptosis 18:1426–1436

    CAS  PubMed  Google Scholar 

  • Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaeth D (2012) Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clinic Oncol 30:2718–2724

    CAS  Google Scholar 

  • Bansal Y, Silakari O (2014) Multifunctional compounds: smart molecules for multifactorial diseases. Eur J Med Chem 76:31–42

    CAS  PubMed  Google Scholar 

  • Bastien D, Hanna R, Leblanc V, Asselin E, Bérube G (2013) Synthesis and preliminary in vitro biological evaluation of 7α-testosterone-chlorambucil hybrid designed for the treatment of prostate cancer. Eur J Med Chem 64:442–447

    CAS  PubMed  Google Scholar 

  • Baviskar AT, Banerjee UC, Gupta M, Singh R, Kumar S, Gupta MK, Kumar S, Raut SK, Khullar M, Singh S, Kumar R (2013) Synthesis of imine-pyrazolopyrimidinones and their mechanistic interventions on anticancer activity. Bioorg Med Chem 21:5782–5793

    CAS  PubMed  Google Scholar 

  • Bello E, Taraboletti G, Colella G, Zucchetti M, Forestieri D, Licandro SA, Berndt A, Richter P, D’Incalci M, Cavalletti E (2013) The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breast cancer xenografts. Mol Cancer Ther 12:131–140

    CAS  PubMed  Google Scholar 

  • Belluti F, Fontana G, Bo LD, Carenini N, Giommarelli C, Zunino F (2010) Design, synthesis and anticancer activities of stilbene-coumarin hybrid compounds: identification of novel proapoptotic agents. Bioorg Med Chem 18:3543–3550

    CAS  PubMed  Google Scholar 

  • Bolognesi ML (2013) Polypharmacology in a single drug: multitarget drugs. Curr Med Chem 20:1639–1645

    CAS  PubMed  Google Scholar 

  • Boorjian SA, Tindall DJ (2013) Management of Prostate Cancer. Springer, Berlin

    Google Scholar 

  • Caffo O, Sava T, Comploj E, Giampaolo MA, Segati R (2010) Estramustine plus docetaxel as second-line therapy in patients with hormone-refractory prostate cancer resistant to docetaxel alone. Urol Oncol: Semin Ori 28:152–156

    CAS  Google Scholar 

  • Cai X, Zhai H-X, Wang J, Forrester J, Qu H, Yin L, Lai C-J, Bao R, Qian C (2010) Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J Med Chem 53:2000–2009

    CAS  PubMed  Google Scholar 

  • Center NC (2013) Cancer facts and figures

  • Chabner BA, Longo DL (2011). Wolters Kluwer Health

  • Chakraborty C (2013) Sirtuins family-recent development as a drug target for aging, metabolism, and age related diseases. Curr Drug Targets 14:666–675

    CAS  PubMed  Google Scholar 

  • Chang C, Lee S, Yeh S, Chang T (2013) Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast, and liver. Oncogene 1:1–10

    Google Scholar 

  • Chauhan M, Kumar R (2013) Medicinal attributes of pyrazolo [3, 4-d] pyrimidines: a review. Bioorg Med Chem 21:5657–5668

    CAS  PubMed  Google Scholar 

  • Chen L, Pankiewicz KW (2007) Recent development of IMP dehydrogenase inhibitors for the treatment of cancer. Curr Opin Drug Discov Devel 10:403

    CAS  PubMed  Google Scholar 

  • Chen J-B, Chern T-R, Wei T–T, Chen C–C, Lin J-H, Fang J-M (2013) Design and synthesis of dual-action inhibitors targeting histone deacetylases and 3-Hydroxy-3-methylglutaryl coenzyme A reductase for cancer treatment. J Med Chem 56:3645–3655

    CAS  PubMed  Google Scholar 

  • Croteau R, Kutchan TM, Lewis NG (2000) Natural products (secondary metabolites). Biochem Mol Niol Plants 24:1250–1318

    Google Scholar 

  • Daniel C, Rauch C (2013) Molecular mechanisms of tumor cell resistance to chemotherapy. Springer, London

    Google Scholar 

  • Delcuve GP, Khan DH, Davie JR (2013) Targeting class I histone deacetylases in cancer therapy. Expert Opin Ther Pat 17:29–41

    CAS  Google Scholar 

  • Denny WA (2001) DNA minor groove alkylating agents. Curr Med Chem 8:533–544

    CAS  PubMed  Google Scholar 

  • Descoteaux C, Brasseur K, Leblanc V, Parent S, Asselin E, Berube G (2012) Design of novel tyrosine-nitrogen mustard hybrid molecules active against uterine, ovarian and breast cancer cell lines. Steroids 77:403–412

    CAS  PubMed  Google Scholar 

  • Di Bussolo V, Minutolo F (2011) Curaxins: a new family of non-genotoxic multitargeted anticancer agents. Chem Med Chem 6:2133–2136

    PubMed  Google Scholar 

  • Diana P, Martorana A, Barraja P, Montalbano A, Dattolo G, Cirrincione G, Dall’Acqua F, Salvador A, Vedaldi D, Basso G (2008) Isoindolo [2, 1-a] quinoxaline derivatives, novel potent antitumor agents with dual inhibition of tubulin polymerization and topoisomerase I. J Med Chem 51:2387–2399

    CAS  PubMed  Google Scholar 

  • Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham D, Lambert D (2009) Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile. Br J Anaesth 103:38–49

    CAS  PubMed  Google Scholar 

  • Do TKT, Hadji-Minaglou F, Antoniotti S, Fernandez X (2014) Secondary metabolites isolation in natural products chemistry: comparison of two semipreparative chromatographic techniques (high pressure liquid chromatography and high performance thin-layer chromatography). J Chromatogr A 1325:256–260

    CAS  PubMed  Google Scholar 

  • Dun B, Sharma A, Teng Y, Liu H, Purohit S, Xu H, Zeng L, She J-X (2013) Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways. PLoS One 8:e81702

    PubMed Central  PubMed  Google Scholar 

  • Fan P, Griffith OL, Agboke F, Anur P, Zou X, McDaniel RE, Creswell K, Kim SH, Katzenellenbogen JA, Gray JW (2013) c-Src modulates estrogen-induced stress and apoptosis in estrogen-deprived breast cancer cells. Cancer Res 73:4510–4520

    CAS  PubMed Central  PubMed  Google Scholar 

  • Favia AD, Cavalli A, Masetti M, Carotti A, Recanatini M (2006) Three-dimensional model of the human aromatase enzyme and density functional parameterization of the iron-containing protoporphyrin IX for a molecular dynamics study of heme-cysteinato cytochromes. Protein Struct Funct Bioinfo 62:1074–1087

    CAS  Google Scholar 

  • Flinn IW, Oki Y, Copland A, Fattaey A, Lai C-J, Laliberte R, Voi M, Berdeja JG (2013) A first-in-man phase 1 study of CUDC-907, a first-in-class chemically-designed dual inhibitor of PI3 K and HDAC in patients with refractory or relapsed lymphoma and multiple myeloma. Blood 122:4363

    Google Scholar 

  • Folger O, Jerby L, Frezza C, Gottlieb E, Ruppin E, Shlomi T (2011) Predicting selective drug targets in cancer through metabolic networks. Mol Syst Biol 7:1–10

    Google Scholar 

  • Fortin S, Berube G (2013) Advances in the development of hybrid anticancer drugs. Expert Opin Invest Drugs 8:1–19

    Google Scholar 

  • Fukuda T, Goebel J, Thøgersen H, Maseck D, Cox S, Logan B, Sherbotie J, Seikaly M, Vinks AA (2011) Inosine monophosphate dehydrogenase (IMPDH) activity as a pharmacodynamic biomarker of mycophenolic acid effects in pediatric kidney transplant recipients. J Clin Pharmacol 51:309–320

    CAS  PubMed Central  PubMed  Google Scholar 

  • Garcia-Beltran O, Areche C, Cassels BK, Cuca Suarez LE (2014) Coumarins isolated from Esenbeckia alata (rutaceae). Biochem Syst Ecol 52:38–40

    CAS  Google Scholar 

  • Gasparian AV, Burkhart CA, Purmal AA, Brodsky L, Pal M, Saranadasa (2011) Curaxins: anticancer compounds that simultaneously suppress NF-kB and activate p53 by targeting fact. Sci Transl Med 3:1–12

    Google Scholar 

  • Gediya LK, Njar VC (2009) Promise and challenges in drug discovery and development of hybrid anticancer drugs. Expert Opin Invest Drugs 4:1099–1111

    CAS  Google Scholar 

  • Glander P, Hambach P, Liefeldt L, Budde K (2012) Inosine 5′-monophosphate dehydrogenase activity as a biomarker in the field of transplantation. Clin Chim Acta 413:1391–1397

    CAS  PubMed  Google Scholar 

  • Guerrant W, Patil V, Canzoneri JC, Oyelere AK (2012) Dual targeting of histone deacetylase and topoisomerase II with novel bifunctional inhibitors. J Med Chem 55:1465–1477

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta A, Saha P, Descoteaux C, Leblanc V, Asselin E, Berube G (2010) Design, synthesis and biological evaluation of estradiol–chlorambucil hybrids as anticancer agents. Bioorg Med Chem Lett 20:1614–1618

    CAS  PubMed  Google Scholar 

  • Hainaut P, Plymoth A (2013) Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer therapy. Curr Opin Oncol 25:50–51

    PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  • Hanamura T, Niwa T, Nishikawa S, Konno H, Gohno T, Tazawa C, Kobayashi Y, Kurosumi M, Takei H, Yamaguchi Y (2013) Androgen metabolite-dependent growth of hormone receptor-positive breast cancer as a possible aromatase inhibitor-resistance mechanism. Breast Cancer Res Treat 139:731–740

    CAS  PubMed  Google Scholar 

  • Hernandez-Guzman FG, Higashiyama T, Pangborn W, Osawa Y, Ghosh D (2003) Structure of human estrone sulfatase suggests functional roles of membrane association. J Biol Chem 278:22989–22997

    CAS  PubMed  Google Scholar 

  • Hulsman N, Medema JP, Bos C, Jongejan A, Leurs R, Smit MJ, de Esch IJ, Richel D, Wijtmans M (2007) Chemical insights in the concept of hybrid drugs: the antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin. J Med Chem 50:2424–2431

    CAS  PubMed  Google Scholar 

  • Ji Y, Li K, Xiao X, Zheng S, Xu T, Chen S (2012) Effects of propranolol on the proliferation and apoptosis of hemangioma-derived endothelial cells. J Pediatr Surg 47:2216–2223

    PubMed  Google Scholar 

  • Jin F, Gao D, Zhang C, Liu F, Chu B, Chen Y, Chen YZ, Tan C, Jiang Y (2013) Exploration of 1-(3-chloro-4-(4-oxo-4H-chromen-2-yl) phenyl)-3-phenylurea derivatives as selective dual inhibitors of Raf1 and JNK1 kinases for anti-tumor treatment. Bioorg Med Chem 21:824–831

    CAS  PubMed  Google Scholar 

  • Johnson CA, Padget K, Austin CA, Turner BM (2001) Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. J Biol Chem 276:4539–4542

    CAS  PubMed  Google Scholar 

  • Khan S, Lopez-Dee Z, Kumar R, Ling J (2013) Activation of NFkB is a novel mechanism of pro-survival activity of glucocorticoids in breast cancer cells. Cancer Lett 337:90–95

    CAS  PubMed  Google Scholar 

  • Kiselev KV (2011) Perspectives for production and application of resveratrol. Appl Microbiol Biotechnol 90:417–425

    CAS  PubMed  Google Scholar 

  • Ko KS, Steffey ME, Brandvold KR, Soellner MB (2013) Development of a chimeric c-Src kinase and HDAC inhibitor. ACS Med Chem Lett 4:779–783

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lai C-J, Bao R, Tao X, Wang J, Atoyan R, Qu H, Wang D-G, Yin L, Samson M, Forrester J (2010) CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity. Cancer Res 70:3647–3656

    CAS  PubMed  Google Scholar 

  • Lin K, Lasater E, Stewart W, Damon LE, Kasarskis A, Bashir A, Pendleton M, Sebra R, Perl AE, Le MH (2013) Preclinical and clinical resistance mechanisms to the investigational selective FLT3 inhibitor PLX3397 in FLT3-ITD + acute myeloid leukemia (AML). Blood 122:3938

    Google Scholar 

  • Lipinski CA (2004) Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Tech 1:337–341

    CAS  Google Scholar 

  • Lunardi A, Ala U, Epping MT, Salmena L, Clohessy JG, Webster KA, Wang G, Mazzucchelli R, Bianconi M, Stack EC (2013) A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet 45:747–755

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mahboobi S, Sellmer A, Winkler M, Eichhorn E, Pongratz H, Ciossek T, Baer T, Maier T, Beckers T (2010) Novel chimeric histone deacetylase inhibitors: a series of lapatinib hybrides as potent inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and histone deacetylase activity. J Med Chem 53:8546–8555

    CAS  PubMed  Google Scholar 

  • Mahoney S, Arfuso F, Rogers P, Hisheh S, Brown D, Millward M, Dharmarajan A (2012) Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines. J Biosci 37:73–84

    CAS  PubMed  Google Scholar 

  • Marchion DC, Bicaku E, Daud AI, Richon V, Sullivan DM, Munster PN (2004) Sequence-specific potentiation of topoisomerase II inhibitors by the histone deacetylase inhibitor suberoylanilide hydroxamic acid. J Cell Biochem Suppl 92:223–237

    CAS  Google Scholar 

  • Marks PA (2010) The clinical development of histone deacetylase inhibitors as targeted anticancer drugs. Expert Opin Invest Drugs 19:1049–1066

    CAS  Google Scholar 

  • Melisi D, Piro G, Tamburrino A, Carbone C, Tortora G (2013) Rationale and clinical use of multitargeting anticancer agents. Curr Opin Pharmacol 13:536–542

    CAS  PubMed  Google Scholar 

  • Merkel D, Filanovsky K, Gafter-Gvili A, Vidal L, Aviv A, Gatt ME, Silbershatz I, Herishanu Y, Arad A, Tadmor T (2013) Predicting infections in high-risk patients with myelodysplastic syndrome/acute myeloid leukemia treated with azacitidine: aretrospective multicenter study. Am J Hematol 88:130–134

    CAS  PubMed  Google Scholar 

  • Messina M, Barnes S (1991) The role of soy products in reducing risk of cancer. J Natl Cancer Inst 83:541–546

    CAS  PubMed  Google Scholar 

  • Meunier B (2007) Hybrid molecules with a dual mode of action: dream or reality? Acc Chem Res 41:69–77

    PubMed  Google Scholar 

  • Molina AM, Hutson TE, Larkin J, Gold AM, Wood K, Carter D, Motzer R, Michaelson MD (2014) A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC). Cancer Chemother Pharmacol 73:181–189

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morgentaler A (2006) Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 50:935–939

    CAS  PubMed  Google Scholar 

  • Morphy R, Rankovic Z (2005) Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem 48:6523–6543

    CAS  PubMed  Google Scholar 

  • Nepali K, Sharma S, Sharma M, Bedi P, Dhar K (2014) Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur J Med Chem 77:422–487

    CAS  PubMed  Google Scholar 

  • Noguchi M, Kakuma T, Uemura H, Nasu Y, Kumon H, Hirao Y, Moriya F, Suekane S, Matsuoka K, Komatsu N (2010) A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer. Cancer Immunol Immunother 59:1001–1009

    CAS  PubMed  Google Scholar 

  • Nussbaumer P, Billich A (2004) Steroid sulfatase inhibitors. Med Res Rev 24:529–576

    CAS  PubMed  Google Scholar 

  • Pandeya SN, Smitha S, Jyoti M, Sridhar SK (2005) Biological activities of isatin and its derivatives. Acta Pharm 55:27–46

    CAS  PubMed  Google Scholar 

  • Park S, Chapuis N, Bardet V, Tamburini J, Gallay N, Willems L, Knight Z, Shokat K, Azar N, Viguie F (2008) PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia 22:1698–1706

    CAS  PubMed  Google Scholar 

  • Pastor N, Domínguez I, Orta ML, Campanella C, Mateos S, Cortés F (2012) The DNA topoisomerase II catalytic inhibitor merbarone is genotoxic and induces endoreduplication. Mutat Res-Fund Mol M 738–739:45–51

    Google Scholar 

  • Patrick GL (2009) An introduction to medicinal chemistry. Oxford University Press Inc, New York

    Google Scholar 

  • Picus J, Halabi S, Kelly WK, Vogelzang NJ, Whang YE, Kaplan EB, Stadler WM, Small EJ (2011) A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer. Cancer 117:526–533

    CAS  PubMed Central  PubMed  Google Scholar 

  • Polynesia (2012) UMU applied for screening herb and plant extracts or pure phytochemicals for antimutagenic activity. Pharma Biol 50:537–610

    Google Scholar 

  • Proudfoot JR (2005) The evolution of synthetic oral drug properties. Bioorg Med Chem Lett 15:1087–1090

    CAS  PubMed  Google Scholar 

  • Pursell N, Ma A, Atoyan R, Samson M, Borek M, DellaRocca S, Yin L, Wang D-g, Zifcak B, Xu G-x (2013) CUDC-907, a Dual HDAC and PI3 K inhibitor, potentially targets cancer cells and the microenvironment in hematological malignancies. Blood 122:4930

    Google Scholar 

  • Rangwala S, Zhang C, Duvic M (2012) HDAC inhibitors for the treatment of cutaneous T-cell lymphomas. Futur Med Chem 4:471–486

    CAS  Google Scholar 

  • Ravery V, Fizazi K, Oudard S, Drouet L, Eymard JC, Culine S, Gravis G, Hennequin C, Zerbib M (2011) The use of estramustine phosphate in the modern management of advanced prostate cancer. BJU Int 108:1782–1786

    CAS  PubMed  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA-Cancer J Clin 62:10–29

    PubMed  Google Scholar 

  • Singer AC, Crowley DE, Thompson IP (2003) Secondary plant metabolites in phytoremediation and biotransformation. Trends Biotech 21:123–130

    CAS  Google Scholar 

  • Sintchak MD, Nimmesgern E (2000) The structure of inosine 5′-monophosphate dehydrogenase and the design of novel inhibitors. Immunopharmacology 47:163–184

    CAS  PubMed  Google Scholar 

  • Solomon VR, Hu C, Lee H (2009) Hybrid pharmacophore design and synthesis of isatin-benzothiazole analogs for their anti-breast cancer activity. Bioorg Med Chem 17:7585–7592

    CAS  PubMed  Google Scholar 

  • Solomon VR, Hu C, Lee H (2010) Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: a hybrid pharmacophore approach. Bioorg Med Chem 18:1563–1572

    CAS  PubMed  Google Scholar 

  • Stanway SJ, Delavault P, Purohit A, Woo LL, Thurieau C, Potter BV, Reed MJ (2007) Steroid sulfatase: a new target for the endocrine therapy of breast cancer. Oncologist 12:370–374

    CAS  PubMed  Google Scholar 

  • Su B, Zhong B, Chennamaneni S, lama R, Yi X, Geldenhuys WJ, Pink JJ, Dowlati A, Xu Y, Zhou A (2013) Synthesis and anti-cancer mechanism investigation of dual Hsp27 and tubulin inhibitors. J Med Chem 56:5306–5320

    PubMed  Google Scholar 

  • Suzuki T, Nakata T, Miki Y, Kaneko C, Moriya T, Ishida T, Akinaga S, Hirakawa H, Kimura M, Sasano H (2003) Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma. Cancer Res 63:2762–2770

    CAS  PubMed  Google Scholar 

  • Takebe N, Cheng X, Fandy TE, Srivastava RK, Wu S, Shankar S, Bauer K, Shaughnessy J, Tricot G (2006) IMP dehydrogenase inhibitor mycophenolate mofetil induces caspase-dependent apoptosis and cell cycle inhibition in multiple myeloma cells. Mol Cancer Ther 5:457–466

    CAS  PubMed  Google Scholar 

  • Tan J, Cang S, Ma Y, Petrillo RL, Liu D (2010) Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol 3:1–13

    Google Scholar 

  • Thurn KT, Thomas S, Moore A, Munster PN (2011) Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer. Future Oncol 7:263–283

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tili E, Michaille J–J (2011) Resveratrol, microRNAs, inflammation, and cancer. J Nucleic Acids 2011:1–9

    Google Scholar 

  • Tsai S-C, Valkov N, Yang W-M, Gump J, Sullivan D, Seto E (2000) Histone deacetylase interacts directly with DNA topoisomerase II. Nat Genet 26:349–353

    CAS  PubMed  Google Scholar 

  • Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615–2623

    CAS  PubMed  Google Scholar 

  • Viegas-Junior C, Danuello A, da Silva Bolzani V, Barreiro EJ, Fraga CAM (2007) Molecular hybridization: a useful tool in the design of new drug prototypes. Curr Med Chem 14:1829–1852

    CAS  PubMed  Google Scholar 

  • Wang JC (1996) DNA topoisomerases. Annu Rev Biochem 65:635–692

    CAS  PubMed  Google Scholar 

  • Wang J, Pursell NW, Samson MES, Atoyan R, Ma AW, Selmi A, Xu W, Cai X, Voi M, Savagner P (2013) Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor, in treating drug resistance and preventing cancer cell migration and invasion. Mol Cancer Ther 12:925–936

    CAS  PubMed  Google Scholar 

  • Wermuth C-G, Ganellin CR, Lindberg P, Mitscher LA (1998) Glossary of terms used in medicinal chemistry (IUPAC recommendations 1997). Annu Rep Med Chem 33:385–395

    CAS  Google Scholar 

  • Woo LL, Sutcliffe OB, Bubert C, Grasso A, Chander SK, Purohit A, Reed MJ, Potter BV (2003) First dual aromatase-steroid sulfatase inhibitors. J Med Chem 46:3193–3196

    CAS  PubMed  Google Scholar 

  • Woo LL, Bubert C, Sutcliffe OB, Smith A, Chander SK, Mahon MF, Purohit A, Reed MJ, Potter BV (2007) Dual aromatase-steroid sulfatase inhibitors. J Med Chem 50:3540–3560

    CAS  PubMed  Google Scholar 

  • Wood PM, Woo L, Humphreys A, Chander SK, Purohit A, Reed MJ, Potter BV (2005) A letrozole-based dual aromatase–sulphatase inhibitor with in vivo activity. J Steroid Biochem Mol Biol 94:123–130

    CAS  PubMed  Google Scholar 

  • Wright AS, Thomas LN, Douglas RC, Lazier CB, Rittmaster RS (1996) Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat. J Clin Invest 98:2558

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao CF, Tao LY, Sun HY, Wei W, Chen Y, Fu LW, Zou Y (2010) Design, synthesis and antitumor activity of a series of novel coumarin-stilbene hybrids, the 3-arylcoumarins. Chin Chem Lett 21:1295–1298

    CAS  Google Scholar 

  • Yance D (2010) Cancer and Inflammation: the emerging role of botanical compounds in targeting proinflammatory pathways, with particular attention to the NFκB signaling pathway. Diakses Tanggal 6:1–22

    Google Scholar 

  • Yang S-Y (2010) Pharmacophore modeling and applications in drug discovery: challenges and recent advances. Drug Discov Today 15:444–450

    CAS  PubMed  Google Scholar 

  • Yee EM, Pasquier E, Iskander G, Wood K, Black DS, Kumar N (2013) Synthesis of novel isoflavene-propranolol hybrids as anti-tumor agents. Bioorg Med Chem 21:1652–1660

    CAS  PubMed  Google Scholar 

  • Zhang M-Q, Wilkinson B (2007) Drug discovery beyond the ‘rule-of-five’. Curr Opin Biotech 18:478–488

    CAS  PubMed  Google Scholar 

  • Zhang X, Su M, Chen Y, Li J, Lu W (2013) The design and synthesis of a new class of RTK/HDAC dual-targeted inhibitors. Molecules 18:6491–6503

    CAS  PubMed  Google Scholar 

  • Zhang Q, Wen C, Xiang Z, Ma J, Wang X (2014) Determination of CUDC-101 in rat plasma by liquid chromatography mass spectrometry and its application to a pharmacokinetic study. J Pharm Biomed Anal 90:134–138

    CAS  PubMed  Google Scholar 

  • Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G (2013) Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 39:74–88

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are thankful to DST Grant (SR/FT/CS-71/2011) for the financial support to the present work. We are also thankful to Prof. P. Ramarao, Dean Academic Affairs, and Acting Vice Chancellor, Central University of Punjab, Bathinda for his constant encouragement.

Author information

Authors and Affiliations

  1. Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, CUPB Library Communication No. P48/14, Bathinda, 151 001, Punjab, India

    Anil Rana, Jimi Marin Alex, Monika Chauhan, Gaurav Joshi & Raj Kumar

Authors
  1. Anil Rana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jimi Marin Alex
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monika Chauhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gaurav Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raj Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raj Kumar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rana, A., Alex, J.M., Chauhan, M. et al. A review on pharmacophoric designs of antiproliferative agents. Med Chem Res 24, 903–920 (2015). https://doi.org/10.1007/s00044-014-1196-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1196-5

Keywords

Search

Navigation