Syntheses, in vitro urease inhibitory activities of urea and thiourea derivatives of tryptamine, their molecular docking and cytotoxic studies

Kanwal,; Khan, Majid; Arshia,; Khan, Khalid Mohammed; Parveen, Shabana; Shaikh, Muniza; Fatima, Narjis; Choudhary, Muhammad Iqbal

doi:10.1016/j.bioorg.2018.10.070

Cited by 30 publications

(12 citation statements)

References 31 publications

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“…1‐(2‐(1H‐indol‐3‐yl)ethyl)‐3‐(2,6‐dimethylphenyl)thiourea (6 af) : Beige solid, m.p. 174–175 °C (water; ref [87] . 184–186 °C); 1 H‐NMR: (500 MHz, CDCl 3 , ref [87] ) δ 7.93 (bs, 1H), 7.53 (d, J =7.9 Hz, 1H), 7.33 (d, J =8.1 Hz, 1H), 7.22−7.11 (m, 3H), 7.07 (d, J =7.5 Hz, 1H), 7.02 (d, J =7.5 Hz, 2H), 6.78 (s, 1H), 5.41 (bs, 1H), 3.91 (q, J =6.4 Hz, 2H), 2.99 (q, J =6.8 Hz, 2H), 2.08 (s, 6H) ppm; 13 C‐NMR: (125 MHz, CDCl 3 ) δ 137.4, 136.6, 132.8, 129.1, 127.2, 122.5, 122.1, 119.8, 118.8, 112.5, 111.3, 45.4, 25.0, 18.0 ppm.…”

Section: Methodsmentioning

confidence: 99%

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Chromatography‐Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur

et al. 2020

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The development of a new three-component chromatographyfree reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.

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Section: Methodsmentioning

confidence: 99%

“…[85] ) δ 7.77 (bs, 1H), 7. [87] 184-186°C); 1 H-NMR: (500 MHz, CDCl 3 , ref [87] [88] 138-140°C); 1 H-NMR: (500 MHz, CDCl 3 , ref. [88] ) δ 7.…”

Section: -Benzyl-3-(4-methoxyphenyl)thiourea (6 Ga)mentioning

confidence: 99%

Chromatography‐Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur

et al. 2020

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“…EX has been reported as an anticancer agent against breast cancer, therefore, the synthesized co-crystal was first evaluated in vitro to observe any changes in its anti-cancer activity against the MCF-7 breast cancer cell line; however, it was found to be ineffective. On the other hand, the coformer (thiourea) is reported as a tested standard to check urease inhibition activity in vitro (Kanwal et al, 2018). Therefore, both the API (EX) and the synthesized co-crystal (EX:TH) were evaluated for their urease enzyme inhibition activity (in vitro) and interesting results were obtained.…”

Section: Biological Activitymentioning

confidence: 99%

“…Unfortunately, the synthesized exemestane:thiourea (EX:TH) (1:1) co-crystal was found to be inactive for anti-cancer activity evaluated against the breast cancer cell line. The discouraging results regarding anti-cancer activity prompted us to evaluate the synthesized co-crystal against urease inhibition activity as our co-former (thiourea) is already reported to be a tested standard in urease inhibition assays (Kanwal et al, 2018). Synthesized co-crystals were found to be several folds more active than tested standard thiourea.…”

Section: Introductionmentioning

confidence: 99%

Crystal engineering of exemestane to obtain a co-crystal with enhanced urease inhibition activity

Fatima

Kumar

Choudhary

et al. 2020

Int Union Crystallogr J

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Co-crystallization is a phenomenon widely employed to enhance the physiochemical and biological properties of active pharmaceutical ingredients (APIs). Exemestane, or 6-methylideneandrosta-1,4-diene-3,17-dione, is an anabolic steroid used as an irreversible steroidal aromatase inhibitor, which is in clinical use to treat breast cancer. The present study deals with the synthesis of cocrystals of exemestane with thiourea by liquid-assisted grinding. The purity and homogeneity of the exemestane-thiourea (1:1) co-crystal were confirmed by single-crystal X-ray diffraction followed by thermal stability analysis on the basis of differential scanning calorimetry and thermogravimetric analysis. Detailed geometric analysis of the co-crystal demonstrated that a 1:1 co-crystal stoichiometry is sustained by N-HÁ Á ÁO hydrogen bonding between the amine (NH 2 ) groups of thiourea and the carbonyl group of exemestane. The synthesized co-crystal exhibited potent urease inhibition activity in vitro (IC 50 = 3.86 AE 0.31 mg ml À1 ) compared with the API (exemestane), which was found to be inactive, and the co-former (thiourea) (IC 50 = 21.0 AE 1.25 mg ml À1 ), which is also an established tested standard for urease inhibition assays in vitro. The promising results of the present study highlight the significance of cocrystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients. Furthermore, the role of various hydrogen bonds in the crystal stability is successfully analysed quantitatively using Hirshfeld surface analysis.

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“…Accordingly, the inhibition of AChE and BChE is considered as a significant neuroprotective target in discovery of AD drugs [6]. Urease, an enzyme of family amidohydrolases, is responsible for the urea hydrolysis into ammonia and CO2 or carbamate [7,8]. The over-expression of urease lead to various adverse health effects including cryptococcosis, tuberculosis, yersiniosis, peptic ulcers and urolithiasis, thus inhibition of urease by the potent urease inhibitors has recently attracted scientific attention [8].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Predictions of Drug-Likeness and Pharmacokinetic Properties of Some Chiral Thioureas as Potent Enzyme Inhibition Agents

2021

Turk J Chem

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A series of chiral thioureas (1-17) were synthesized from and tested for their anticholinesterase, tyrosinase and urease enzyme inhibitor activities. Various phenylisothiocyanates were added to solution of ʟ-cysteine in methanol:water (1:1 v/v) at room temperature and stirred for 24h. Precipitated solid was recrystallized from nbutanol. Pure compounds were characterized by NMR ( 1 H and 13 C), FTIR and CHNS. Tertiary amine containing N-(4-(diethylamino)phenyl)-N'-(2-mercapto-1carboxyethanyl)thiourea 17, N-(4-(dimethylamino)phenyl)-N'-(2-mercapto-1carboxyethanyl)thiourea 16 and trimethoxy containing N-(3,4,5-trimethoxyphenyl)-N'-(2-mercapto-1-carboxyethanyl)thiourea 14 were more active than galantamine against AChE and BChE enzymes. In tyrosinase enzyme inhibition activity, compound 14, 10, 12, 6, 13, and 11 exhibited higher tyrosinase inhibitory activity showing IC50 values of 1.1±0.1, 1.5±0.3, 1.6±0.6, 1.9±0.5, 2.2±0.9 and 2.9±0.2 mM, respectively. In urease enzyme inhibition activity assay, 17 showed higher activity. This work demonstrates the pharmacological significance of chiral thiourea derivatives synthesized from ʟ-cysteine and showing their potential. There is a need to perform more in vitro and in vivo biological activities followed by clinical trials to bring such thiourea to the market.

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Syntheses, in vitro urease inhibitory activities of urea and thiourea derivatives of tryptamine, their molecular docking and cytotoxic studies

Cited by 30 publications

References 31 publications

Chromatography‐Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur

Chromatography‐Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur

Crystal engineering of exemestane to obtain a co-crystal with enhanced urease inhibition activity

Synthesis, Predictions of Drug-Likeness and Pharmacokinetic Properties of Some Chiral Thioureas as Potent Enzyme Inhibition Agents

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