Synthesis, ADMET Prediction, and Antitumor Profile of Phenoxy-hydrazine-1,3-thiazoles Derivatives

被引：0

作者：

de Siqueira, Lucianna Rabelo Pessoa ^{[1
,2
]}

Ferreira, Larissa Pelagia de Lima ^{[1
,2
]}

de Oliveira Filho, Gevanio Bezerra ^{[1
]}

de Oliveira, Marcos Victor Gregorio ^{[1
]}

Pinto, Aline Ferreira ^{[1
]}

de Melo Silva, Vanessa Gouveia ^{[1
]}

Gomes, Paulo Andre Teixeira de Moraes ^{[1
]}

Cardoso, Marcos Verissimo de Oliveira ^{[3
]}

Soeiro, Maria de Nazare Correia ^{[4
]}

dos Santos, Flaviana Alves ^{[2
]}

Pitta, Maira Galdino da Rocha ^{[2
]}

Nunes, Janine Siqueira ^{[1
]}

Rego, Moacyr Jesus Barreto de Melo ^{[2
]}

Leite, Ana Cristina Lima ^{[1
]}

机构：

[1] Univ Fed Pernambuco, Ctr Hlth Sci, Dept Pharmaceut Sci, Lab Planning Med Chem, BR-50740520 Recife, PE, Brazil

[2] Univ Fed Pernambuco, Therapeut Innovat Res Ctr, Recife, PE, Brazil

[3] Univ Pernambuco, Lab Prospection Bioact Mol, BR-56328903 Petrolina, PE, Brazil

[4] Fiocruz MS, Inst Oswaldo Cruz, Lab Cell Biol, Ave Brasil 4365, BR-21040900 Rio De Janeiro, Brazil

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2023年 / 23卷 / 04期

关键词：

1; 3-Thiazoles; Bioisosterism; Cancer; DU145; MOLT-4; Antitumor; ANTICANCER ACTIVITY; THIAZOLE; THIOSEMICARBAZONES; CANCER; POTENT; AGENTS;

D O I：

10.2174/1568026623666221226090807

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Background: Cancer is one of the most important barriers to increasing life expectancy in all countries in the 21st century. Investigations of new anti-cancer drugs with low side effects are an urgent demand for medicinal chemists. Considering the known antitumor and immunomodulatory activity of thiazoles, this work presents the synthesis and antineoplastic activity of new thiazoles. Methods: The 22 new compounds (2a-v) were synthesized from different thiosemicarbazones and 2-bromoacetophenone. The compounds were evaluated on: MOLT-4, HL-60, HL-60/MX1, MM1S, SKMEL-28, DU145, MCF-7, and T47d. Results: Compound 2b induced cellular viability on MOLT-4 (37.1%), DU145 (41.5%), and HL-60/MX1 (58.8%) cells. On MOLT-4 cells, compound 2b exhibited an IC50 of 8.03 mu M, and against DU145 cells, an IC50 of 6.04 mu M. Besides, at IC50 and fold of IC50, 20% to 30% of dead cells were found, most due to necrosis/late apoptosis. Most compounds no showed cytotoxicity against fibroblast cells L929 at the concentrations tested. The compound did not alter the cell cycle of DU145 cells when compared to the negative control. Therefore, compound 2b stands out against DU145 and MOLT-4 cells. Conclusion: Our study reinforced the importance of 1,3-thiazoles nuclei in antitumor activity. In addition, derivative 2b stands out against DU145 and MOLT-4 cells and could be a starting point for developing new antineoplastic agents.

引用

页码：265 / 282

页数：18

共 50 条

[41] Heteropolyacid anchored on SBA-15 functionalized with 2-aminoethyl dihydrogen phosphate: a novel and highly efficient catalyst for one-pot, three-component synthesis of trisubstituted 1,3-thiazoles
Jahanshahi, Roya
Akhlaghinia, Batool
RESEARCH ON CHEMICAL INTERMEDIATES, 2018, 44 (04) : 2451 - 2474
[42] Facile synthesis of new N1-alkylated 1H-indazole-3-carboxamide derivatives as potential anticancer agents: In vitro, ADMET prediction, and SAR studies
Puri, Sachin
Juvale, Kapil
JOURNAL OF MOLECULAR STRUCTURE, 2022, 1269
[43] Design, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives bearing 1,3-thiazole moiety as novel anti-inflammatory EGFR inhibitors with cardiac safety profile
Abdel-Aziz, Salah A.
Taher, Ehab S.
Lan, Ping
Asaad, Gihan F.
Gomaa, Hesham A. M.
El-Koussi, Nawal A.
Youssif, Bahaa G. M.
BIOORGANIC CHEMISTRY, 2021, 111
[44] Novel 1,3-oxathiole derivatives: Efficient one-pot synthesis, antitumor efficiency, X-ray crystallographic, Hirshfeld surface, and Fukui function analysis
Bin Muhsinah, Abdullatif
Kheder, Nabila A.
Soliman, Saied M.
Ghabbour, Hazem A.
Elhaty, Ismail A.
Gad, Nehad H.
Mabkhot, Yahia N.
JOURNAL OF MOLECULAR STRUCTURE, 2025, 1331
[45] Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design, synthesis, anticonvulsant evaluation, ADMET profile and molecular docking
El-Helby, Abdel-Ghany A.
Ayyad, Rezk R. A.
El-Adl, Khaled
Elkady, Hazem
MOLECULAR DIVERSITY, 2019, 23 (02) : 283 - 298
[46] Quinazolin-4-one derivatives lacking toxicity-producing attributes as glucokinase activators: design, synthesis, molecular docking, and in-silico ADMET prediction
Khadse, Saurabh C.
Amnerkar, Nikhil D.
Dave, Manasi U.
Lokwani, Deepak K.
Patil, Ravindra R.
Ugale, Vinod G.
Charbe, Nitin B.
Chatpalliwar, Vivekanand A.
FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES, 2019, 5 (01)
[47] Design, one-pot synthesis, in silico ADMET prediction and molecular docking of novel triazolyl thiadiazine and thiazole derivatives with evaluation of antimicrobial, antioxidant and antibiofilm inhibition activity
Khidre, Rizk E.
Sabry, Eman
El-Sayed, Ahmed F.
Sediek, Ashraf A.
JOURNAL OF THE IRANIAN CHEMICAL SOCIETY, 2023, 20 (12) : 2923 - 2947
[48] Design, one-pot synthesis, in silico ADMET prediction and molecular docking of novel triazolyl thiadiazine and thiazole derivatives with evaluation of antimicrobial, antioxidant and antibiofilm inhibition activity
Rizk E. Khidre
Eman Sabry
Ahmed F. El-Sayed
Ashraf A. Sediek
Journal of the Iranian Chemical Society, 2023, 20 : 2923 - 2947
[49] Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme
El-Helby, Abdel-Ghany A.
Sakr, Helmy
Ayyad, Rezk R. A.
El-Adl, Khaled
Ali, Mamdouh M.
Khedr, Fathalla
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2018, 18 (08) : 1184 - 1196
[50] Synthesis, ADMET prediction and reverse screening study of 3,4,5-trimethoxy phenyl ring pendant sulfur-containing cyanopyrimidine derivatives as promising apoptosis inducing anticancer agents
Nainwal, Lalit Mohan
Shaququzzaman, Mohammad
Akhter, Mymoona
Husain, Asif
Parvez, Suhel
Khan, Farah
Naematullah, Md.
Alam, Mohammad Mumtaz
BIOORGANIC CHEMISTRY, 2020, 104

← 1 2 3 4 5 →