Computational and Experimental Insights into Pharmacological Potential: Synthesis, In Vitro Evaluation, and Molecular Docking Analysis of Bioactive Urea and Thiourea Derivatives.

This study delves into the synthesis, in vitro assessment, and molecular docking analysis of bioactive urea and thiourea derivatives, which have gained attention in pharma chemistry due to their versatile chemical reactivity and potential therapeutic applications. One pot synthetic methodology was employed to create a diverse class of compounds. Subsequent in vitro assessments, including antimicrobial assays, unveiled the pharmacological potential of these derivatives, offering insights into their ability to inhibit pathogenic microorganisms.

Synthesis, molecular docking study and biological evaluation of new pyrrole scaffolds as potential antitubercular agents for dual targeting of enoyl ACP reductase and dihydrofolate reductase.

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties.

New thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids: Synthesis, MCF-7 inhibition and binding studies.

Two synthetic methods were proposed for the preparation of a new series of thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids (TOT-1 to 15) and their structures were elucidated based on spectral data. Studies on cytotoxicity, ROS, cellular uptake and interactions of TOT-14 with calf thymus DNA were carried out. Anticancer activity of compounds, TOT-1 to 15 on breast cancer (MCF-7) cell lines was investigated.

Synthesis, molecular simulation studies, in vitro biological assessment of 2-substituted benzoxazole derivatives as promising antimicrobial agents.

The 2-substituted benzoxazole derivatives are known to exhibit a wide spectrum of biological potential. Two series of novel benzoxazole derivatives containing 2-phenyl and 2-N-phenyl groups were synthesized, by following the green chemistry approach. All the newly synthesized derivatives were screened against gram-positive bacteria (, ), gram-negative bacteria (, and the fungus (.

Synthesis, Molecular Docking Study, and Biological Evaluation of New 4-(2,5-Dimethyl-1-pyrrol-1-yl)-'-(2-(substituted)acetyl)benzohydrazides as Dual Enoyl ACP Reductase and DHFR Enzyme Inhibitors.

In this study, a new series of 4-(2,5-dimethyl-1-pyrrol-1-yl)--(2-(substituted)acetyl) benzohydrazides () were prepared and new heterocycles underwent thorough characterization and evaluation for antibacterial activity; some of them underwent further testing for in vitro inhibition of enoyl ACP reductase and DHFR enzymes. The majority of the synthesized molecules exhibited appreciable action against DHFR and enoyl ACP reductase enzymes. Some of the synthesized compounds also showed strong antibacterial and antitubercular properties.

WELPSA: A natural catalyst of alkali and alkaline earth metals for the facile synthesis of tetrahydrobenzo[]pyrans and pyrano[2,3-]pyrimidinones as inhibitors of SARS-CoV-2.

Since 2019, the infection of SARS-CoV-2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[]pyran and pyrano[2,3-]pyrimidinones as SARS-CoV-2 inhibitors via three-component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. Lemon peel from juice factory waste, namely, lemon (), sweet lemon (), and Kaffir lime or Citron (), effectually utilized to obtain WELPSA, WESLPSA, and WEKLPSA, respectively, for the synthesis of title compounds.

Synthesis of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives as potential glucosidase inhibitors.

Background: A hybrid molecule of different biologically active substances can improve affinity and efficiency compared to a standard drug. Hence based on this fact, we predict that a combination of fluorine, oxadiazole, sulfur, etc., may enhance α-glucosidase inhibition activity compared to a standard drug.

Green synthesis of therapeutically active 1,3,4-oxadiazoles as antioxidants, selective COX-2 inhibitors and their in silico studies.

A modest, competent and green synthetic procedure for novel coumarinyl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t has been reported. Analysis of the docked (PDB ID: 5IKR; A-Chain) poses of the compounds illustrated that they adopt identical conformations to the extremely selective COX-2 inhibitor. The biological outcomes as well as computational study suggested that the compounds originated to have elevated resemblance towards COX-2 enzyme than COX-1.

Microwave assisted regioselective synthesis of quinoline appended triazoles as potent anti-tubercular and antifungal agents via copper (I) catalyzed cycloaddition.

Quinolin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4H)-ones 8j-v were synthesized by click chemistry as an ultimate tactic where [3 + 2] cycloaddition of azides with terminal alkynes has been evolved. Herein, we are inclined to divulge the implication and prevalence of CuSO·5HO and THF/water promoted [3 + 2] cycloaddition reactions. The foremost supremacy of this method are transitory reaction times, facile workup, excellent yields (88-92%) with exorbitant purity and regioselective single product formation both under conventional and microwave method.

Synthesis, molecular docking studies, and in vitro antimicrobial evaluation of piperazine and triazolo-pyrazine derivatives.

For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by H NMR, C NMR, IR, and mass spectrometry techniques. To further confirm the chemical identity of the adducts, a crystal of N-{[(4-chlorophenyl)-3-(trifluoromethyl)]-5,6-dihydro-[1,2,4]triazolo[4,3-a]}pyrazine-7(8H)-carboxamide (3t) was prepared and analyzed using X-ray crystallography.

Novel 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles as glycogen phosphorylase inhibitors: An in vivo antihyperglycemic activity study.

In this study, we report the ring transformation of 3-arylsydnone into 1-aryl-1H-pyrazole-3-carbonitriles via [3 + 2] cycloaddition with acrylonitrile. 1-Aryl-1H-pyrazole-3-carbonitrile underwent [2 + 3] cycloaddition with sodium azide to afford 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles which were further subjected to N-alkylation with aryl/heteroaryl alkyl halides to afford 1,5- and 2,5-disubstituted tetrazoles. Furthermore, the title compounds were screened for in vivo antihyperglycemic activity using albino Wistar rats of either sex.

New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies.

A series of new urea derivatives, containing aryl moieties as potential antimicrobial agents, were designed, synthesized, and characterized by H NMR, C NMR, FT-IR, and LCMS spectral techniques. All newly synthesized compounds were screened in vitro against five bacterial strains ( and ) and two fungal strains ( and ). Variable levels of interaction were observed for these urea derivatives.

Design, synthesis, and molecular docking study of new piperazine derivative as potential antimicrobial agents.

Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by H NMR, C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis.

A click chemistry approach for the synthesis of cyclic ureido tethered coumarinyl and 1-aza coumarinyl 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis H37Rv and their in silico studies.

Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4/7/10 have been obtained by the reaction of 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c).

Click chemistry based regioselective one-pot synthesis of coumarin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4H)-ones as newer potent antitubercular agents.

Coumarin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4H)-ones (8k-z) were synthesized via copper(I)-catalyzed azide-alkyne cycloaddition click chemistry. The synthesized hybrid molecules were characterized by spectral studies. Compounds 8k-z were screened for their in vitro anti-TB activity by using the Microplate Alamar Blue assay and for cytotoxicity using the MTT assay.

Synthesis, molecular docking studies, and antimicrobial evaluation of new structurally diverse ureas.

A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using H NMR, C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction.

Graph theoretical analysis, in silico modeling, prediction of toxicity, metabolism and synthesis of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl) phenyl) quinazolin-4(3H)-ones as NMDA receptor inhibitor.

Hit, Lead & Candidate Discovery A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d-aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects.

Synthesis, molecular modeling and BACE-1 inhibitory study of tetrahydrobenzo[b] pyran derivatives.

β-Secretase (BACE1) has been broadly documented as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synthesis of tetrahydrobenzo [b] pyrans was carried out by condensing aromatic aldehyde, malononitrile and 1,3-cyclohexanedione using ionic liquid 1-butyl-3-methyl imidazolium chloride ([bmIm]Cl) in aqueous alcohol media.

Pharmacophore mapping, molecular docking, chemical synthesis of some novel pyrrolyl benzamide derivatives and evaluation of their inhibitory activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis.

In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway.

Design Graph Theoretical Analysis and Modeling of Biomass Encapsulated N-Succinyl Chitosan Nanoparticles for Enhanced Anticancer Activity.

Purpose: To investigate N-succinyl chitosan nanoparticles (NSC NPs) encapsulation with biomass for high utilization enhanced effectiveness and least side effects for anticancer activity.

Methods: The potential bioactive compounds from D. bardawil biomass were encapsulated NSC NPs by ionotropic gelation method and to characterize its molecular shape, particle size, stability and polydispersity index using FTIR, XRD, SEM, TEM and Zetasize Nano analyzer.

Functionalization of 3-chloroformylcoumarin to coumarin Schiff bases using reusable catalyst: an approach to molecular docking and biological studies.

Recently, heterogeneous catalysts have been explored eximiously in the synthesis of heterocyclic compounds. Therefore, here we used solid-supported heterogeneous silica sulfuric acid as a catalyst for the synthesis of Schiff's base of 3-chloroformylcoumarin in view of simplified procedure, reusability and acceptable efficiency, which are required in organic synthesis. An efficient and facile methodology is preferred for synthesis of a class of chromeno-3-substituted derivatives () with good yields.

Molecular docking studies and facile synthesis of most potent biologically active N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide hybrids: An approach for microwave-assisted syntheses and biological evaluation.

An efficient, high yields and rapid synthesis of N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide derivatives (4a-4j) under microwave-irradiation has been described. All the newly synthesized compounds (4a-4j) were characterized by elemental analysis and spectroscopic studies. The synthesised compounds (4a-4j) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method.

Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents.

A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis HRv, anti-microbial activity in vitro against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacterias (Escherichia coli, Salmonella typhi) as well as fungi (Candida albicans). The compound (3a) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL.

Pyrrolyl Pyrazoline Carbaldehydes as Enoyl-ACP Reductase Inhibitors: Design, Synthesis and Antitubercular Activity.

Introduction: In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes.

Method & Materials: Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase from , which plays an important role in FAS-II biosynthetic pathway of and also it is an important target for designing novel anti-TB agents.

Results: Among the synthesized compounds, compounds and showed H-bonding interactions with MET98, TYR158 and co-factor NAD, all of which fitted well within the binding pocket of InhA.