13250-46-9Relevant academic research and scientific papers
Synthesis and evaluation of the anticancer activity of [Pt(diimine)(N,N-dibutyl-N′-acylthiourea)]+complexes
Peega, Tebogo,Magwaza, Rachael N.,Harmse, Leonie,Kotzé, Izak A.
, p. 11742 - 11762 (2021/09/06)
Despite the concerted efforts to develop targeted cancer treatments, these therapies are plagued by the rapid development of resistance and serious adverse drug reactions. Based on the wide clinical use and successes of the platinum drugs like cisplatin and oxaliplatin, we investigated the synthesis and potential anticancer efficacy of alternative platinum complexes. A series of nine cationic square planar platinum(ii) complexes were synthesized and characterized and then evaluated for their anticancer activity. The complexes were of the type [Pt(diimine)(Ln-κO,S)]+where diimine is either 1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (dmp) or dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) and Ln-κO,Srepresenting variousN,N-dibutyl-N′-acylthiourea ligands. The anticancer activity of the synthesised complexes was evaluated against two lung cancer cell lines (A549 and H1975) and a colorectal cancer cell line, HT-29. The 50% inhibitory concentrations (IC50) for the most cytotoxic compounds were determined and the mode of cell death evaluated. The structure-activity relationships indicated that complexes with the 5,6-dimethyl-1,10-phenanthroline variation of the diimine ligand were the most active against the cell lines tested, while the activity of complexes based on the acylthiourea ligand varied between the cell lines. IC50values for the three active platinum complexes were in the low micromolar range for the three cell lines and ranged between 0.68 μM and 2.28 μM. Changes to cell morphology indicate that the active platinum complexes induce cell death by both apoptosis and paraptosis. The complexes were able to induce the nuclear expression of the cyclin-dependent kinase inhibitor, p21, which is an indicator of DNA damage. The collective data indicate that these platinum complexes are valuable lead compounds for further analysis and cancer drug discovery.
1,2,4-Thiadiazole acyclic nucleoside phosphonates as inhibitors of cysteine dependent enzymes cathepsin K and GSK-3β
Pomeislová, Alice,Otmar, Miroslav,Rube?ová, Petra,Beny?ek, Jakub,Matou?ová, Marika,Mertlíková-Kaiserová, Helena,Pohl, Radek,Po?tová Slavětínská, Lenka,Pomeisl, Karel,Kre?merová, Marcela
, (2021/01/18)
In analogy to antiviral acyclic nucleoside phosphonates, a series of 5-amino-3-oxo-1,2,4-thiadiazol-3(2H)-ones bearing a 2-phosphonomethoxyethyl (PME) or 3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) group at the position 2 of the heterocyclic moiety has be
Impact of aliphatic acyl and aromatic thioamide substituents on the anticancer activity of Ru(ii)-: P -cymene complexes with acylthiourea ligands - In vitro and in vivo studies
Balakrishnan, Nithya,Bhuvanesh, Nattamai,Echeverria, Cesar,Gayathri, Dasararaju,Haribabu, Jebiti,Karvembu, Ramasamy,Mohamed Subarkhan, Mohamed Kasim,Swaminathan, Srividya
, p. 16311 - 16325 (2021/11/27)
Six different acylthiourea ligands (L1-L6) and their corresponding Ru(ii)-p-cymene complexes (P1-P6) were designed to explore the structure-activity relationship of the complexes upon aliphatic chain and aromatic conjugation on the C- and N-terminals, res
Design, Synthesis, and Insecticidal Activity of Novel Doramectin Derivatives Containing Acylurea and Acylthiourea Based on Hydrogen Bonding
Bai, Ping,Cheng, Yao,Lu, Xiaoxia,Yang, Jian,Zhang, Qi,Zheng, Cheng
, p. 5806 - 5815 (2020/06/19)
Our recent investigation on the insecticidal activities of several doramectin derivatives preliminarily revealed that the presence of hydrogen bonds at the C4″ position of the molecule with target protein γ-aminobutyric acid (GABA) receptor was crucial for retaining high insecticidal activity. As a continuation of our research work on the development of new insecticides, two series of novel acylurea and acylthiourea doramectin derivatives were designed and synthesized. The bioassay results indicated that the newly synthesized compounds (5o, 5t, and 6t) exhibited higher insecticidal activity against diamondback moth, oriental armyworm, and corn borer than the control compounds doramectin, commercial avermectins, chlorbenzuron, and lead compound 3g in our laboratory. Specifically, compound 5t was identified as the most promising insecticide against diamondback moth, with a final mortality rate of 80.00% at the low concentration of 12.50 mg/L, showing approximately 7.75-fold higher potency than the parent doramectin (LC50 value of 48.1547 mg/L), 6.52-fold higher potency than commercial avermectins (LC50 value of 40.5507 mg/L), and 3.98-fold higher potency than compound 3g (LC50 value of 24.7742 mg/L). Additionally, molecular docking simulations revealed that compound 5t (2.17, 2.20, 2.56, and 2.83 ?) displayed stronger hydrogen-bond action in binding with the GABA receptor, better than that of compound 5o (1.64 and 2.15 ?) and compound 6t (2.20 and 2.31 ?) at the C4″ position. This work demonstrated that these compounds containing hydrogen-bond groups might contribute to the improvement of insecticidal activity and supply certain hints toward structure optimization design for the development of new insecticides.
Design, green synthesis, molecular docking and anticancer evaluations of diazepam bearing sulfonamide moieties as VEGFR-2 inhibitors
Saleh, Nashwa M.,El-Gaby, Mohamed S.A.,El‐Adl, Khaled,Abd El-Sattar, Nour E.A.
, (2020/10/18)
Novel series of diazepam bearing sulfonamide moieties 5a-f and 7a-c were designed, synthesized and evaluated for anticancer activity against HepG2, HCT-116 and MCF-7 cell lines. MCF-7 was the most sensitive cell line to the influence
Synthesis, inhibition studies against AChE and BChE, drug-like profiling, kinetic analysis and molecular docking studies of N-(4-phenyl-3-aroyl-2(3H)-ylidene) substituted acetamides
Larik, Fayaz Ali,Saeed, Aamer,Faisal, Muhammad,Hamdani, Salma,Jabeen, Farukh,Channar, Pervaiz Ali,Mumtaz, Amara,Khan, Imtiaz,Kazi, Mahar Ali,Abbas, Qamar,Hassan, Mubashir,Korabecny, Jan,Seo, Sung-Yum
, (2019/12/09)
Halogenated and non-halogenated N-(4-phenyl-3-aroyl-2(3H)-ylidene) substituted acetamides were prepared by base-catalyzed cyclization of corresponding acetyl thioureas with phenacyl bromide. The synthesized compounds were structurally characterized by 1H NMR and 13C NMR spectroscopy and were screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Molecular docking studies, drug-like profiling and kinetic analysis were performed to further investigate the inhibition mechanism of the compounds. This study provided useful insights into the design and development of novel dual inhibitors, in addition to understanding the mechanism by which such drugs interact with targets and exert their biochemical action. All the compounds showed superior inhibition profile compared to the standards possessing sub-micromolar and micromolar IC50 values for AChE and BChE, respectively. Docking simulations revealed that the compound 6g showed strong binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained as the best docked poses showed important binding features mostly based on interactions due to aromatic moieties and oxygen atoms of the compound. Cation-pi/pi-pi interactions together with hydrogen bond forces were the key players responsible for ligand anchoring in the active sites. The striking results accomplished both in docking computations and experimental findings ascertained that the compound 6g can serve as a scaffold for both AChE and BChE inhibition.
Novel N-(benzo[d]oxazol-2-yl)alkanamides; synthesis and carbonic anhydrase II inhibition studies
Saeed, Aamer,Channar, Pervaiz A.,Arshad, Muhammad,El-Seedi, Hesham R.,Abbas, Qamar,Hassan, Mubashir,Raza, Hussain,Seo, Sung-Yum
, p. 2831 - 2843 (2020/05/25)
Carbonic anhydrase (CA II) inhibitors are very important therapeutic targets in drug design for treatment of neuropathic pain and in eradication of glaucoma, cancer, epilepsy, ulcer and obesity. In this study, some two2-substituted benzoxazoles (3a-j) wer
3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively inhibit the tumor-associated carbonic anhydrase isoform IX over the off-target isoforms I, II and IV
Fattah, Tanzeela Abdul,Bua, Silvia,Saeed, Aamer,Shabir, Ghulam,Supuran, Claudiu T.
, p. 123 - 128 (2018/10/20)
We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a–k) acting as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5–44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35–37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.
Synthesis, Characterization, and Computional Studies of Triazatetracyclo Acetamide
Odame,Hosten,Tshentu
, p. 1804 - 1809 (2019/01/14)
N-[(9E)-8,0 10,0 17-triazatetracyclo[8.7.0.02,7.011,18]heptadeca-1(17),2(7),3,5,11,13,15-heptaen-9-ylidene] acetamide (I) is synthesized and characterized by spectroscopy, microanalysis, and single crystal X-ray diffractometry. Compound 1 crystallizes in the monoclinic space group P21/n with a = 17.5552(17) ?, b = 4.6163(4) ?, c = 17.7662(17) ?, β = 115.953(3)°, and Z = 4. The bond angles and bond lengths of the compound are computed using the density functional theory with B3LYP, BPW91, and wB97XD functionals and the 6-31G++(d,p) basis set. The frontier orbitals that contribute to the reactivity of triazatetracyclics are discussed.
Synthesis of sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors, pharmacokinetic properties, lead optimization, Lineweaver-Burk plot evaluation and binding analysis
Sajid-ur-Rehman,Saeed, Aamer,Saddique, Gufran,Ali Channar, Pervaiz,Ali Larik, Fayaz,Abbas, Qamar,Hassan, Mubashir,Raza, Hussain,Fattah, Tanzeela Abdul,Seo, Sung-Yum
, p. 3707 - 3715 (2018/06/19)
To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containin
