Synthesis, cytotoxic, and carbonic anhydrase inhibitory effects of new 2-(3-(4-methoxyphenyl)-5-(aryl)-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole derivatives

被引:15
作者
Tugrak, Mehtap [1 ]
Gul, Halise Inci [1 ]
Sakagami, Hiroshi [2 ]
Gulcin, Ilhami [3 ]
机构
[1] Ataturk Univ, Fac Pharm, Dept Pharmaceut Chem, Erzurum, Turkey
[2] Meikai Univ, Div Pharmacol, Res Inst Odontol, Sakado, Saitama, Japan
[3] Ataturk Univ, Fac Sci, Dept Chem, Erzurum, Turkey
关键词
MONO MANNICH-BASES; BIOLOGICAL-ACTIVITY; HCA IX; HETEROCYCLES; CHALCONES; DOCKING; DESIGN;
D O I
10.1002/jhet.3985
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
2-(3-[4-Methoxyphenyl]-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazoles (1b-7b) were synthesized for the first time except 1b, and spectral methods such as H-1 NMR, C-13 NMR and HRMS were utilized to illuminate the chemical structures of the synthesized compounds. Phenyl (1b), 2-methoxyphenyl (2b), 4-methoxyphenyl (3b), 4-methoxy-3-hydroxyphenyl (4b), 2,5-dimethoxyphenyl (5b), 3,4,5-trimethoxyphenyl (6b), or thiophene-2-yl (7b) was used as a aryl part. The inhibitory effects of the compounds were evaluated toward human carbonic anhydrase I and II enzymes (hCA I and hCA II). In vitro cytotoxic effects of the compounds against human oral squamous carcinomas and human normal oral cells were carried out via MTT. The compounds (1b-7b) had Ki values of 36.87 +/- 11.62-66.24 +/- 2.99 mu M (hCA I) and 22.66 +/- 1.41-89.95 +/- 6.25 mu M (hCA II). Compounds 1b (Ki = 36.87 +/- 11.62 mu M) toward hCA I, 6b (Ki = 22.66 +/- 1.41 mu M) toward hCA II had significant enzyme inhibitory potency. Compound 6b had the highest tumor selectivity (TS = 29.3) and potency selectivity expression (PSE = 272.3) values. Therefore, compounds 1b and 6b with CAs inhibition effect and compound 6b with the cytotoxicity may be forwarded to further studies as potent compounds.
引用
收藏
页码:2762 / 2768
页数:7
相关论文
共 36 条
[1]   Synthesis and antifungal activity of some s-mercaptotriazolobenzothiazolyl amino acid derivatives [J].
Aboelmagd, A. ;
Ali, Ibrahim A. I. ;
Salem, Ezzeldin M. S. ;
Abdel-Razik, M. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 60 :503-511
[2]   Design and synthesis of novel stiripentol analogues as potential anticonvulsants [J].
Aboul-Enein, Mohamed N. ;
El-Azzouny, Aida A. ;
Attia, Mohamed I. ;
Maklad, Yousreya A. ;
Amin, Kamilia M. ;
Abdel-Rehim, Mohamed ;
El-Behairy, Mohammed F. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 47 :360-369
[3]   Synthesis of novel 5-amino-1,3,4-thiadiazole-2-sulfonamide containing acridine sulfonamide/carboxamide compounds and investigation of their inhibition effects on human carbonic anhydrase I, II, IV and VII [J].
Aday, Burak ;
Ulus, Ramazan ;
Tanc, Muhammet ;
Kaya, Muharrem ;
Supuran, Claudiu T. .
BIOORGANIC CHEMISTRY, 2018, 77 :101-105
[4]   Synthesis and Carbonic Anhydrase Inhibitory Effects of Novel Sulfamides Derived from 1-Aminoindanes and Anilines [J].
Akbaba, Yusuf ;
Bastem, Enes ;
Topal, Fevzi ;
Gulcin, Ilhami ;
Maras, Ahmet ;
Goksu, Suleyman .
ARCHIV DER PHARMAZIE, 2014, 347 (12) :950-957
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   Facile synthesis of some pyrazoline-based compounds with promising anti-inflammatory activity [J].
Eid, Nahed M. ;
George, Riham F. .
FUTURE MEDICINAL CHEMISTRY, 2018, 10 (02) :183-199
[7]   Design, synthesis, biological evaluation and docking studies of new 3-(4,5-dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole derivatives as potent antioxidants and 15-lipoxygenase inhibitors [J].
ElBordiny, Haydi Saher ;
El-Miligy, Mostafa Mahmoud ;
Kassab, Shaymaa Emam ;
Daabees, Hoda ;
El-Hawash, Soad Abdelhamid Mohamed ;
Ali, Waleed Ali Mohamed .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 145 :594-605
[8]   Synthesis, Cytotoxicity Evaluation, Molecular Docking and Utility of Novel Chalcones as Precursors for Heterocycles Incorporating Pyrazole Moiety [J].
Gomha, Sobhi M. ;
Abdallah, Magda A. ;
Abbas, Ikhlass M. ;
Kazem, Mariam S. H. .
MEDICINAL CHEMISTRY, 2018, 14 (04) :344-355
[9]   Synthesis and Cytotoxicities of New Azafluorenones with Apoptotic Mechanism of Action and Cell Cycle Analysis [J].
Gul, Halise Inci ;
Tugrak, Mehtap ;
Gul, Mustafa ;
Sakagami, Hiroshi ;
Umemura, Naoki ;
Anil, Baris .
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2018, 18 (12) :1770-1778
[10]   Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes [J].
Gul, Halise Inci ;
Yamali, Cem ;
Bulbuller, Merve ;
Kirmizibayrak, Petek Ballar ;
Gul, Mustafa ;
Angeli, Andrea ;
Bua, Silvia ;
Supuran, Claudiu T. .
BIOORGANIC CHEMISTRY, 2018, 78 :290-297