Design, Synthesis and Cytotoxic Activity Evaluation of Newly Synthesized Amides-Based TMP Moiety as Potential Anticancer Agents over HepG2 Cells

被引:7
作者
Al-Warhi, Tarfah [1 ]
Aldhahrani, Adil [2 ]
Althobaiti, Fayez [3 ]
Fayad, Eman [3 ]
Abu Ali, Ola A. [4 ]
Albogami, Sarah [3 ]
Abu Almaaty, Ali H. [5 ]
Khedr, Amgad I. M. [6 ]
Bukhari, Syed Nasir Abbas [7 ]
Zaki, Islam [8 ]
机构
[1] Princess Nourah Bint Abdulrahman Univ, Dept Chem, Coll Sci, POB 84428, Riyadh 11671, Saudi Arabia
[2] Taif Univ, Turabah Univ Fac, Clin Lab Sci Dept, Taif 21995, Saudi Arabia
[3] Taif Univ, Dept Biotechnol, Fac Sci, POB 11099, Taif 21944, Saudi Arabia
[4] Taif Univ, Dept Chem, Coll Sci, POB 11099, Taif 21944, Saudi Arabia
[5] Port Said Univ, Fac Sci, Zool Dept, Port Said 42526, Egypt
[6] Port Said Univ, Dept Pharmacognosy, Fac Pharm, Port Said 42526, Egypt
[7] Jouf Univ, Dept Pharmaceut Chem, Coll Pharm, Sakaka 72388, Saudi Arabia
[8] Port Said Univ, Fac Pharm, Pharmaceut Organ Chem Dept, Port Said 42526, Egypt
关键词
diamide; triamide; tetraamide; TMP; HDAC; tubulin; Annexin V; caspase; MMP; DERIVATIVES; INHIBITORS;
D O I
10.3390/molecules27123960
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC50 values 0.65 and 0.92 mu M, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of caspase 3/7. Caspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of caspase 3/7 may occur via mitochondrial apoptotic pathway.
引用
收藏
页数:16
相关论文
共 32 条
[1]   Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation [J].
Aboeldahab, Alshimaa M. A. ;
Beshr, Eman A. M. ;
Shoman, Mai E. ;
Rabea, Safwat M. ;
Aly, Omar M. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 146 :79-92
[2]   Recent developments of HDAC inhibitors: Emerging indications and novel molecules [J].
Bondarev, Andrey D. ;
Attwood, Misty M. ;
Jonsson, Jorgen ;
Chubarev, Vladimir N. ;
Tarasov, Vadim V. ;
Schioth, Helgi B. .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2021, 87 (12) :4577-4597
[3]   Design and Synthesis of Some New Furan-Based Derivatives and Evaluation of In Vitro Cytotoxic Activity [J].
Bukhari, Syed Nasir Abbas ;
Ejaz, Hasan ;
Elsherif, Mervat A. ;
Junaid, Kashaf ;
Zaki, Islam ;
Masoud, Reham E. .
MOLECULES, 2022, 27 (08)
[4]   Discovery of DNA-Targeting HDAC Inhibitors with Potent Antitumor Efficacy In Vivo That Trigger Antitumor Immunity [J].
Chen, Chen ;
Li, Xue ;
Zhao, Huajun ;
Liu, Meng ;
Du, Jintong ;
Zhang, Jian ;
Yang, Xinying ;
Hou, Xuben ;
Fang, Hao .
JOURNAL OF MEDICINAL CHEMISTRY, 2022, 65 (04) :3667-3683
[5]   CC-01 (chidamide plus celecoxib) modifies the tumor immune microenvironment and reduces tumor progression combined with immune checkpoint inhibitor [J].
Chen, Jia-Shiong ;
Chou, Cheng-Han ;
Wu, Yi-Hong ;
Yang, Mu-Hsuan ;
Chu, Sz-Hao ;
Chao, Ye-Su ;
Chen, Chia-Nan .
SCIENTIFIC REPORTS, 2022, 12 (01)
[6]  
Dhiman A., 2022, ACTA PHARM SIN B
[7]   Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes [J].
Doke, Mayur ;
Pendyala, Gurudutt ;
Samikkannu, Thangavel .
PLOS ONE, 2021, 16 (06)
[8]   Cracking a cancer code histone deacetylation in epigenetic: the implication from molecular dynamics simulations on efficacy assessment of histone deacetylase inhibitors [J].
Dushanan, Ramachandren ;
Weerasinghe, Samantha ;
Dissanayake, Dhammike P. ;
Senthilinithy, Rajendram .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2022, 40 (05) :2352-2368
[9]   A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization [J].
Ebenezer, Oluwakemi ;
Shapi, Michael ;
Tuszynski, Jack A. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (07)
[10]   Design, synthesis, and biological evaluation of novel nicotinamide derivatives as potential histone deacetylase-3 inhibitors [J].
Hamoud, Mohamed M. S. ;
Pulya, Sravani ;
Osman, Nermine A. ;
Bobde, Yamini ;
Hassan, Abdalla E. A. ;
Abdel-Fattah, Hanan A. ;
Ghosh, Balaram ;
Ghanim, Amany M. .
NEW JOURNAL OF CHEMISTRY, 2020, 44 (23) :9671-9683