Synthesis, Antiproliferative Evaluation, and Molecular Docking Study of Novel Longifolene‐Derived Tetraline Fused Thiazole‐Amide Derivatives

Twenty novel longifolene‐derived tetraline fused thiazole‐amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT‐IR, NMR, ESI‐MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK‐OV‐3 ovarian cancer cell lines, MCF‐7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T‐24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a–6c displayed significant and broad‐spectrum antiproliferative activity against almost the tested cancer cell lines with IC50 in the range of 7.84 to 55.88 μM, of which compound 6c exhibited excellent antiproliferative activities with 7.84 μM IC50 against SKOV‐3, 13.68 μM IC50 against HepG2, 15.69 μM IC50 against A549, 19.13 μM IC50 against MCF‐7, and 22.05 μM IC50 against T‐24, showing better and broad‐spectrum antiproliferative effect than that of the positive control 5‐FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure‐activity relationships were found and discussed herein by DFT theoretical calculation.

[1]  Vijay Kumar Chattu,et al.  Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019 , 2021, JAMA oncology.

[2]  W. Duan,et al.  Synthesis, Antifungal Activity and 3D‐QSAR Study of Novel ( E )‐Longifolene‐Derived Tetralone Oxime Ethers , 2021 .

[3]  W. Duan,et al.  Synthesis and Antiproliferative Evaluation of Novel Longifolene-Derived Tetralone Derivatives Bearing 1,2,4-Triazole Moiety , 2020, Molecules.

[4]  W. Duan,et al.  Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety , 2020, Chinese Journal of Organic Chemistry.

[5]  A. Deep,et al.  Thiazole-containing compounds as therapeutic targets for cancer therapy. , 2019, European journal of medicinal chemistry.

[6]  W. Duan,et al.  Synthesis and Antiproliferative Evaluation of Novel Hybrids of Dehydroabietic Acid Bearing 1,2,3-Triazole Moiety , 2019, Molecules.

[7]  Patricia A. Quispe,et al.  On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies , 2019, Heliyon.

[8]  Xu Song,et al.  A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. , 2019, European journal of medicinal chemistry.

[9]  H. Bian,et al.  Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmune Arthritis , 2019, Front. Immunol..

[10]  R. Quesada,et al.  Therapeutic strategies involving survivin inhibition in cancer , 2018, Medicinal research reviews.

[11]  M. A. Motaleb,et al.  Rational design and synthesis of new tetralin-sulfonamide derivatives as potent anti-diabetics and DPP-4 inhibitors: 2D & 3D QSAR, in vivo radiolabeling and bio distribution studies. , 2018, Bioorganic chemistry.

[12]  L. Yurttaş,et al.  New Thiazoline-Tetralin Derivatives and Biological Activity Evaluation , 2018, Molecules.

[13]  H. Türkez,et al.  Synthesis and Anticancer Activity of Novel Ureas and Sulfamides Incorporating 1-Aminotetralins. , 2017, Archives of medical research.

[14]  L. Moro,et al.  Mitochondria and cancer chemoresistance. , 2017, Biochimica et biophysica acta. Bioenergetics.

[15]  D. Guillarme,et al.  Antineoplastic drugs and their analysis: a state of the art review. , 2017, The Analyst.

[16]  Shuguang Yuan,et al.  Using PyMOL as a platform for computational drug design , 2017 .

[17]  Wenxia Sun,et al.  Systematic review of ixabepilone for treating metastatic breast cancer , 2017, Breast Cancer.

[18]  Zhengming Li,et al.  Syntheses, biological activities and SAR studies of novel carboxamide compounds containing piperazine and arylsulfonyl moieties. , 2016, European journal of medicinal chemistry.

[19]  Eman M. Raafat,et al.  Synthesis of (3-(naphthalen-1-yl)oxiran-2-yl)(5,6,7,8-tetrahydronaphthalen-2-yl)methanone and reaction with some nucleophiles for anticancer evaluation , 2015, Research on Chemical Intermediates.

[20]  M. Alsaid,et al.  Novel thiophene derivatives with sulfonamide, isoxazole, benzothiazole, quinoline and anthracene moieties as potential anticancer agents , 2014, Acta pharmaceutica.

[21]  A. Gamal-Eldeen,et al.  Induction of intrinsic apoptosis pathway in colon cancer HCT-116 cells by novel 2-substituted-5,6,7,8-tetrahydronaphthalene derivatives. , 2014, European journal of medicinal chemistry.

[22]  S. Saeidnia,et al.  Anti‐proliferative and apoptotic activities of constituents of chloroform extract of Juglans regia leaves , 2014, Cell proliferation.

[23]  H. Awad,et al.  Synthesis, tumor inhibitory and antioxidant activity of new polyfunctionally 2-substituted 5,6,7,8-tetrahydronaphthalene derivatives containing pyridine, thioxopyridine and pyrazolopyridine moieties. , 2013, Acta poloniae pharmaceutica.

[24]  J. Vose,et al.  A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B‐cell lymphoma , 2012, Cancer.

[25]  D. Newton,et al.  The “survivin suppressants” NSC 80467 and YM155 induce a DNA damage response , 2012, Cancer Chemotherapy and Pharmacology.

[26]  G. Giaccone,et al.  A phase II study of YM155, a novel small-molecule suppressor of survivin, in castration-resistant taxane-pretreated prostate cancer. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  Jiamu Du,et al.  Structural basis for recognition of H3T3ph and Smac/DIABLO N-terminal peptides by human Survivin. , 2012, Structure.

[28]  Yanli Jin,et al.  GDP366, a novel small molecule dual inhibitor of survivin and Op18, induces cell growth inhibition, cellular senescence and mitotic catastrophe in human cancer cells , 2010, Cancer biology & therapy.

[29]  N. Neamati,et al.  Combination effects of SC144 and cytotoxic anticancer agents , 2009, Anti-cancer drugs.

[30]  V. Kojić,et al.  Synthesis and Antitumor Activity of New Tiazofurin Analogues Bearing a 2,3-Anhydro Functionality in the Furanose Ring. , 2007 .

[31]  N. K. Sah,et al.  Structural, functional and therapeutic biology of survivin. , 2006, Cancer letters.

[32]  T. Patel,et al.  Pifithrin- (cid:1) Enhances Chemosensitivity by a p38 Mitogen-Activated Protein Kinase-Dependent Modulation of the Eukaryotic Initiation Factor 4E in Malignant Cholangiocytes , 2006 .

[33]  David S. Goodsell,et al.  Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4 , 1996, J. Comput. Aided Mol. Des..