45 research outputs found
Synthesis, Biological Evaluation, and Molecular Dynamics of Carbothioamides Derivatives as Carbonic Anhydrase II and 15-Lipoxygenase Inhibitors
A series of hydrazine-1-carbothioamides derivatives (3a–3j) were synthesized and analyzed for inhibitory potential towards bovine carbonic anhydrase II (b-CA II) and 15-lipoxygenase (15-LOX). Interestingly, four derivatives, 3b, 3d, 3g, and 3j, were found to be selective inhibitors of CA II, while other derivatives exhibited CA II and 15-LOX inhibition. In silico studies of the most potent inhibitors of both b-CA II and 15-LOX were carried out to find the possible binding mode of compounds in their active site. Furthermore, MD simulation results confirmed that these ligands are stably bound to the two targets, while the binding energy further confirmed the inhibitory effects of the 3h compound. As these compounds may have a role in particular diseases, the reported compounds are of great relevance for future applications in the field of medicinal chemistry
Ibuprofen-thiadiazole hybrid compounds: Synthesis, vibrational analysis and molecular structure of 5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine hydrochloride
The ibuprofen derivative 5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine hydrochloride is prepared by via cyclization of ibuprofen with thiosemicarbazide in the presence of POCl3. The compound has been characterized by using FT-IR and multinuclear (1H and 13C) NMR spectroscopies, and elemental analysis. The molecular structure in crystalline phase has been determined by single crystal X-Ray diffraction. The compound crystallizes in the triclinic system with space group P-1 as discrete cations and chloride anions with two enantiomers present in the asymmetric unit. A full vibrational analysis of the FT-IR and FT-Raman spectra has been performed in conjunction with quantum chemical calculations. Experimental data agree with the occurrence of the thiadiazole NH protonated form in the solid phase. The observation of the Îœ(NN) and ÎŽ(CNN) normal modes as strong signals in the infrared and Raman spectra at 1189 (1180âŻcmâ1) and 774âŻcmâ1 suggests a NN bond with partial double bond character in the thiadiazole moiety, in good agreement with the computed values at the B3LYP/6-311++G(d,p) level of approximation. The NBO analysis showed that both, the sulfur lone pair and the exocyclic amine nitrogen lone pair orbitals contribute to strong resonance interactions with the adjacent Ï*(N2=C8) antibonding orbital of the protonated thiadiazole group.Fil: Channar, Pervaiz Ali. Quaid-i-azam University; PakistĂĄnFil: Saeed, Aamer. Quaid-i-azam University; PakistĂĄnFil: Larik, Fayaz Ali. Quaid-i-azam University; PakistĂĄnFil: Bolte, Michael. J.W.-Goethe-UniversitĂ€t; AlemaniaFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino"; Argentin
New 1-octanoyl-3-aryl thiourea derivatives: Solvent-free synthesis, characterization and multi-target biological activities
Exploration of newly synthesized azo-thiohydantoins as the potential alkaline phosphatase inhibitors via advanced biochemical characterization and molecular modeling approaches
Abstract In the current study, Azo-Thiohydantoins derivatives were synthesized and characterized by using various spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, elemental and HRMS analysis. The compounds were evaluated for alkaline phosphatase activity and it was observed that among all the synthesized compounds, derivative 7e exhibited substantial inhibitory activity (IC50â=â0.308â±â0.065 ”M), surpassing the standard inhibitor (LâPhenyl alanine, IC50â=â80.2â±â1.1 ”M). Along with this, these derivatives were comprehensively examined regarding the electronic properties and reactivity of the synthesized compounds using Density Functional Theory (DFT) calculations, where the results were found very promising and the synthesized compound were found stable. After that, SwissADME evaluations highlighted compounds for their favorable physicochemical properties, including solubility and drug-likeness. Molecular docking exhibited the strong binding affinities of 7f and 7e derivatives with intestinal alkaline phosphatase (IAP), further supported by Molecular Dynamics (MD) simulations. This comprehensive integration of experimental and computational approaches sheds the light on the potential therapeutic applications of the synthesized compounds. By providing a detailed investigation of these aspects, this research opens the avenues for the development of novel pharmacologically active compounds with diverse applications
Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking
Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC50 = 0.081 ± 0.003 ”M), 6a (IC50 = 0.0022 ± 0.0002 ”M), 9e (IC50 = 0.0250 ± 0.0007 ”M) and 12d (IC50 = 0.0266 ± 0.0021 ”M) were found to be the lead compounds compared to standard (thiourea, IC50 = 17.814 ± 0.096 ”M). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e, 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a, 12b, 12d, 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C
Synthesis, conformational studies and NBO analysis of (4-chloro-3,5-dimethyl-1H-pyrazol- 1-yl)(p-tolyl)methanone
The title compound (3) was obtained by cyclocondensation of 4-methylbenzohydrazide (2) with 3-chloropentane-2,4-dione (1) in dry ethanol in presence of acetic acid and recrystallization from ethanol. The molecular and crystal structure of the new pyrazole derivative was determined by single crystal X-ray diffraction. It crystallizes in triclinic system with space group P-1. The molecules in the crystal adopt an anti conformation for the mutual orientation of the CO double bond with respect to the NN single bond. The pyrazole and phenyl rings are very far from being coplanar, with a dihedral angle of 49.62(4)°. Additionally, full geometry optimizations and frequency calculations were computed at the B3LYP/6-311++G(d,p) level of approximation. The NBO population analysis showed that the lpp(N1) lone pair orbital contributes to a strong resonance interactions with both adjacent Ï*(N2=C2) and Ï*(C5=C4) antibonding orbitals of the pyrazole group.Fil: Channar, Pervaiz Ali. Quaid-i-azam University; PakistĂĄnFil: Saeed, Aamer. Universidad Quaid-i-azam; PakistĂĄnFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino"; ArgentinaFil: Larik, Fayaz Ali. Quaid-i-azam University; PakistĂĄnFil: Riaz, Saira. Quaid-i-azam University; PakistĂĄnFil: Flörke, Ulrich. Universitat Paderborn; PakistĂĄnFil: Arshad, Muhammad. Quaid-i-azam University; PakistĂĄ
Dual Inhibition of AChE and BChE with the C-5 Substituted Derivative of Meldrumâs Acid: Synthesis, Structure Elucidation, and Molecular Docking Studies
Alzheimerâs disease (AD) lies in the category of those diseases which are still posing challenges to medicinal chemists, and the search for super-effective drugs for the treatment of AD is a work in progress. The inhibition of cholinesterase is considered a viable strategy to enhance the level of acetylcholine in the brain. The C-5 substituted derivative of Meldrumâs acid was synthesized and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activity. The simple and unique structure of synthesized derivative 3 was found to be good for the dual inhibition of both enzymes (AChE and BChE). 2,2-Dimethyl-5-(([2-(trifluoromethyl) phenyl]amino)methylidene)-1,3-dioxane-4,6-dione (3) showed significant inhibition against AChE, with an IC50 value of 1.13 ± 0.03 ” M (Standard Neostigmine 22.2 ± 3.2 ”M), and moderate inhibition against BChE, with an IC50 value of 2.12 ± 1.22 ”M (Standard Neostigmine 49.6 ± 6.11 ”M). The structural insights reveal that compound 3 possesses intriguing reactive groups, which can potentially evoke the non-covalent interactions and possibly assist by binding in the active site of the target protein. Docking simulations revealed that the compound 3 showed 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 oxygen atoms and the aromatic moieties of the compound. The docking computations coupled with the experimental findings ascertained that the compound 3 can serve as a scaffold for the dual inhibitors of the human acetylcholine esterases
Sulfonamide linked ciprofloxacin derivatives as a novel class of inhibitors of jack bean urease. Synthesis of Kinetic mechanism and Bioinformatics
Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC50 = 0.081 ± 0.003 ”M), 6a (IC50 = 0.0022 ± 0.0002 ”M), 9e (IC50 = 0.0250 ± 0.0007 ”M) and 12d (IC50 = 0.0266 ± 0.0021 ”M) were found to be the lead compounds compared to standard (thiourea, IC50 = 17.814 ± 0.096 ”M). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e, 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a, 12b, 12d, 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C
An intramolecular 1,5-chalcogen bond on the conformational preference of carbonyl thiocarbamate species
Two closely related compounds, namely, O-methyl (4-fluorobenzoyl)carbamothioate (I) and O-methyl (4-methylbenzoyl)carbamothioate (II) were prepared in good yields by the reaction of the corresponding benzoyl isothiocyanates and methanol. The structural and conformational properties of both compounds were analyzed using a combined approach including single-crystal X-ray diffraction and quantum chemical calculations. A rich conformational landscape is envisaged for the vacuum-isolated species around the central carbamothioate group, with the pseudo-anti conformation (CO and CS double bonds pointing toward opposite orientations) being the most stable form. The X-ray molecular structure shows the presence of this form in the crystalline phase for both compounds. The occurrence of a 1,5-OâŻO intramolecular short distance was observed, suggesting the relevance of chalcogenâŻchalcogen interactions in the conformational preference. Natural bond orbital population analysis and quantum chemical calculations through an isodesmic reaction scheme were applied to better understand the conformational preference and the nature of the OâŻO intramolecular interactions. The quantum theory of atoms in molecules was also used to examine the electronic densities around the S(5) pseudo-ring formed through the intramolecular interaction in the carbamothioate moiety. Furthermore, the vibrational features were analyzed by measuring the infrared and Raman spectra.Fil: Channar, Pervaiz Ali. Quaid-i-azam University. Department Of Chemistry; PakistĂĄnFil: Saeed, Aamer. Quaid-i-azam University. Department Of Chemistry; PakistĂĄnFil: Larik, Fayaz Ali. Quaid-i-azam University. Department Of Chemistry; PakistĂĄnFil: Flörke, Ulrich. UniversitĂ€t Paderborn. FakultĂ€t fĂŒr Naturwissenschaften. Department Chemie; AlemaniaFil: El-Seedi, Hesham. International Research Center For Food Nutrition And Sa; China. Jiangsu University. International Research Center for Food Nutrition and Safety; ChinaFil: Rodriguez Pirani, Lucas Sebastian. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino"; ArgentinaFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de QuĂmica InorgĂĄnica "Dr. Pedro J. Aymonino"; Argentin
Structure elucidation, DNA binding, DFT, molecular docking and cytotoxic activity studies on novel single crystal (E)-1-(2-fluorobenzylidene)thiosemicarbazide
Compound 3 {(E)-1-(2-fluorobenzylidene)thiosemicarbazide} â a new Schiff base of thiosemicarbazide has been synthesized, characterized and reported for crystal structure. Planer side chain in the crystal structure was observed co-planer with aromatic ring plane and molecules were connected into centrosymmetric dimmers via intermolecular hydrogen bonding. DFT geometry optimization and the relevant quantum parameters indicated unstable and reactive nature of compound 3. Experimental and theoretical findings for DNA binding by UVâvisible, cyclic voltammetry and molecular docking studies showed consistency in kinetic (Kb) and thermodynamic (ÎG) parameters and that compound 3 significantly interacted with DNA via intercalation. Viscometric analysis further comprehended intercalation as possible binding mode of the compound with DNA and non-denaturing of DNA in the presence of 10% aqueous DMSO. Docked parameters further assured the drug like characteristics of the investigated compound as fit in Lipinskiâs criteria. Dose dependant cytotoxic activity of compound 3 against human Huh-7 cell line indicated its anti-cancer potential at 100âŻÂ”g/ml concentration. Keywords: Thiosemicarbazide Schiff base, Crystal structure, DNA binding, DFT calculations, Molecular docking, Huh-7 cell line activit