Chemistry, anti-diabetic activity and structural analysis of substituted dihydropyrimidine analogues (original) (raw)
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Frontiers in Endocrinology
In an attempt to find new targets for α-amylase and α-glucosidase for the treatment of type 2 diabetes mellitus, the present study aims in determining the anti-diabetic potential of synthesized dihydropyrimidinone derivatives. The in vitro α-glucosidase and α-amylase inhibitory activity was performed and the molecular docking analysis of the ligand in the active binding site of target protein was determined. The results revealed significant percent inhibition of α-glucosidase by the compound 6-benzyl-4-(4-hydroxyphenyl)-3,4,6,7-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione (compound A). The active compound showed 81.99% inhibition when compared to standard ascorbic acid having percent inhibition 81.18%. The IC50 of active compound (A) showed to be 1.02 µg/ml. The molecular docking analysis revealed that the ligand bound to the active binding site of protein with the lowest binding energy of -7.9 kcal/mol that was also significantly similar to standard having -7.8 kcal/mol binding...
Microwave-assisted synthesis of bioactive tetrahydropyrimidine derivatives as antidiabetic agents
Folia Medica
Introduction: In drug discovery, pyrimidine analogues show good biological response and many drug moieties have pyrimidine core. Aim: On the basis of prior review, we synthesized a series of N-(substituted phenyl)-1,3,6-trimethyl-4-(4-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)methoxy)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide parade a 1,3,4-oxadiazole core which were evaluated for in vitro antidiabetic screening. Materials and methods: The tetrahydropyrimidine derivatives have been synthesized by microwave irradiation method. It was carried out by Biginelli condensation of 1,3,4-oxadiazole based aldehyde, substituted acetoacetanilide and N,N’-dimethyl urea. All synthesized compounds were evaluated for antidiabetic screening. Results: By the results derived from antidiabetic activity, compounds 4a, 4e, 4g, and 4i show good inhibition compared to others because of electron withdrawing and hydroxyl groups. All results are compared with standard drug acarbose. Conclusions: ...
Microwave Assisted Synthesis of Tetrahydropyrmidine and in Silico Screening of Antidiabetic Drug
International Journal of Current Pharmaceutical Research, 2020
Objective: To detect the microwave-assisted synthesis of Tetrahydropyrimidine derivative and its molecular docking studies for Diabetes. Methods: The Bignelli condensation method was used for Tetrahydropyrimidine derivative synthesis. The docking studies made in Argus Lab software. Results: The Tetrahydropyrimidine is synthesized using the microwave. The Tetrahydropyrimidine derivative is found to be attack the insulin receptor, as it the tendency of binding with insulin receptor showed in Argus lab. Further, the good binding site of Tetrahydropyrimidine derivative with insulin receptor was predicted. Conclusion: From the research work, The Tetrahydropyrimidine derivative shows its affinity to bind with the insulin receptor. The binding value is averagely 7 which indicates it can attraction with the receptor, so it can control Diabetic mellitus by altering insulin secretion in blood plasma.
Dihydropyrimidines are an important class of heterocyclic compounds reported in 1893 for the first time by P.Biginelli and possess wide spectrum of biological properties.Several catalysts have been used for the preparation of dihydropyrimidines but the procedures associated with them are difficult.So this requires a new procedure using a catalyst which is readily available and with easy procedure.The present work overcomes the difficulty by carrying out the synthesis of novel Dihydropyrimidine derivatives using aromatic aldehydes, methylacetoacetate ,thiourea and phosphorous pentoxide. All the synthesized compounds were characterized by IR and 1 H NMR Spectroscopy. The compounds were evaluated for their antibacterial, antifungal and antioxidant activities. IVa and IVd compound show good antimicrobial activities. The compound IVb and IVd have significant antioxidant properties.
International journal of drug delivery technology, 2020
Dihydropyrimidinone and dihydropyrimidine derivatives are reported to possess broad biological activities. Many synthetic samples have been studied as antibacterial, antiviral, and anticancer agents. We decided to synthesize novel compounds of new pyrimidine derivatives. The present work involves the synthesis of new dihydropyridine derivatives. The starting vanillin, compound (1) was used as the key intermediate to prepare the 5-acetyl-4-(4-hydroxy-3-methoxyphenyl)-6-methyl pyrimidine-2(1H)-one(2),Ethyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-oxo-1,2-dihydropyrimidine-5-carboxylate (3), 4-(4-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydro quinazoline-2(1H)-one (4), respectively, through the reaction with urea and acetylacetone or ethyl acetoacetate or cyclohexanone but 4-(4-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydro quinazoline-2(1H)-thione (5) reacted with thiourea and cyclohexanone. FTIR, 1 H-NMRand 13 C-NMR spectroscopy characterized all the synthesized compounds. The synthesized derivatives were screened for their in vitro, antibacterial activity against two gram-positive bacteria: Bacillus subtilis, and Staphylococcus aureus and two gram-negative bacteria: Klebsiella pneumonia and Salmonella typhi and the results showed that most of them have good antibacterial activity. While their antifungal activity against three fungi species: (Aspergillus fumigates, Aspergillus niger, and Rhizopus), revealed that compounds (1-5) displayed the most potent antifungal activity. Density functional theory (DFT) calculations for the synthesized compounds (1-5) were conducted, using a molecular structure with optimized geometry. Highest occupied molecular orbital/lowest unoccupied molecular orbital energies and structures are demonstrated. The antimicrobial activity indicates that compounds 3 and 4 are the most active than the compounds 2 and 5. Molecular docking revealed that compounds (4) and (5), with cyclohexyl groups are important to block the active centers of glucose-6-phosphate synthase in the bacteria and fungi.
2016
SYNTHESIS OF FUNCTIONAL DERIVATIVES OF 3-AMINO-2-R-7-(R'-PHENYL)-3H-THIENO[2,3-d]PYRIMIDINE-4- ONES AND STUDY OF THEIR ANTI-DIABETIC ACTIVITY Ovsjanykova Yu . O ., Sytnik K . M ., Shemchuk L . A ., Zagayko A . L ., Fylymonenko V . P . National University of Pharmacy, Kharkiv Introduction. Synthesis of 3-amino-2-R-7-(R'-phenyl)-3H-thieno[3,2-d] pyrimidine-4-ones was accomplished using interaction between 3-amino-4-(R-phenyl)-tiofen-2-carboxylic acids hydrazides with aliphatic carboxylic acids. The proposed reaction was proved itself as an efficient and convenient method for thienopyrimidine system constructing using available reagents under mild conditions, due to the fact that the obtained compounds contain primary amino group in the 3-d position. The main aim of this work was to study the reactivity of 3-amino-2-R-7-phenyl-3H-thieno[3,2-d]pyrimidine-4-one, to study possible chemical modification of the amino group in the 3-d position and to make an initial pharmacological s...
Bioorganic Chemistry, 2014
A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against a-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC 50 value 112.21 ± 0.97 lM), to show the enzyme-inhibitor interactions.
2000
Eight new 4-Substitutedaryl-6-methyl-2-pyrimidinone-5 - (N-p-tosyl) Carbohydrazides ( c1-8) have been synthesized in a three step reaction. In first step 5-(Ethoxycarbonyl)-6-methyl-4-substitutedaryl-3,4-dihydropyrimidin-2(1H)- ones obtained ( a1-8) and in second step 4-Substitutedaryl-6-methyl-2-pyrimidinone-5-Carbohydrazides (b1-8). Third step involves synthesis of 4-Substitutedaryl-6-methyl-2-pyrimidinone-5-(N-p-tosyl) Carbohydrazides ( c1-8). Their structures are confirmed by IR, 1 H- NMR, C 13 NMR and Mass. The compounds were tested for antihypertensive activity
Synthesis, characterization and biological evaluation of dihydropyrimidine derivatives
Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 2012
A series of dihydropyrimidines containing quinoline were prepared under conventional heating and microwave irradiation. The structures of newly synthesized compounds were established based on analytical and spectral studies. Further these compounds were evaluated for their antioxidant, antifungal and antibacterial activities. Most of the compounds showed moderate to good activity when compared with standard.