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In search of potent inhibitors of cholinesterase enzymes and antioxidant agents, synthetic derivatives of dihydroquinazolin-4(1H)-one (1–38) were evaluated as potential anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitions and radical (DPPH and ABTS) scavenging activities. The structure–activity relationship (SAR) was mainly based on the different substituents at the aryl part which showed a significant effect on the inhibitory potential of enzymes and radical scavenging activities. The kinetic studies of most active compounds showed a noncompetitive mode of inhibition for AChE and a competitive mode of inhibition for the BChE enzyme. Additionally, molecular modelling studies were carried out to investigate the possible binding interactions of quinazolinone derivatives with the active site of both enzymes.

Suzuki coupling reaction is one of the useful methods for carbon‐carbon bond formation. In the present study, the aforementioned method is used to expand an aryl appendage on the indolenine nucleus of diastereomeric syn‐ and anti‐6‐bromo‐4a‐isopropyl‐2‐methyl‐2,3,4,4a‐tetrahydro‐1H‐carbazole analogs. Therefore, two sets of new diastereomeric Suzuki‐coupled products (16 compounds) were prepared. For this, diastereomeric syn‐ and anti‐6‐bromo‐4a‐isopropyl‐2‐methyl‐2,3,4,4a‐tetrahydro‐1H‐carbazole analogs were treated with arylboronic acids in the presence of palladium catalyst under thermal catalysis. Structures of synthesized compounds were inferred using spectroscopic studies. DFT‐based quantum chemical calculations were used to decipher structural attributes and stability of diastereomeric bromo‐2,3,4,4a‐tetrahydro‐1H‐carbazoles and their Suzuki‐coupled products, which revealed chair conformation for methylcyclohexane ring of syn‐compound while twist‐boat conformation for diastereomeric anti‐compound. syn‐Compound was found more stable than its anti‐isomer based on DFT‐calculations. Also, results demonstrated agreement between experimental and theoretical chemical shift values in NMR spectra with some deviations. Thus, structural elucidation based on computational advances in combination with the spectroscopic method can provide a powerful method for studying and comparing the structural attributes of diastereomeric compounds. [ABSTRACT FROM AUTHOR]

α‐Glucosidase inhibition is one of the key targets for controlling diabetes. In consideration of that, new L‐valinol derived fluorinated sultam triazoles were synthesized as α‐glucosidase inhibitors, and their activities were further compared with the precursor molecules (sulfonamides, sultams, and N‐propargyl sultams). Primarily, all the synthesized sultam triazoles and precursor compounds (sulfonamides, sultams, and N‐propargyl sultams) were evaluated for different biological activities, including cytotoxicity, anti‐inflammatory, and α‐glucosidase inhibitory activities. Results revealed that only sultam triazoles exhibited inhibition against α‐glucosidase enzyme (IC50 values: 173 to 194 μM) using acarbose (IC50: 875.85 ± 2.03 μM) as the standard drug. These sultam triazoles were prepared after few steps, starting from enantiopure L‐valinol, which differ electronically (due to the position of fluorine atom and different positions on aromatic ring). Structures of all the compounds were evaluated using different spectroscopic techniques. Kinetics of active compounds were also investigated to find their mode of inhibition. [ABSTRACT FROM AUTHOR]

In this study, a range of oxamide ligands were synthesized by the reaction of amines with oxalyl chloride in basic medium. Spectroscopic and analytical techniques such as IR, 1H-NMR and ESI-MS techniques were used for characterization of the synthesized oxamides. The synthesized oxamides were screened for Lipoxygenase inhibition. Biological screening revealed that the oxamides possessed good lipoxygenase inhibition activities, whereas, the unsubstituted oxamide did not show any distinct lipoxygenase inhibition activity. Molecular docking studies of the oxamides were also carried out for lipoxygenase inhibition. The results obtained from molecular docking were well correlated with the empirical data. [ABSTRACT FROM AUTHOR]

Synthesis of new antioxidants and enzyme inhibitors is an active area of research in pharmaceutical sciences. This can be used for development of new active product ingredients which can prevent body from different diseases. This study comprises of preparation of transition metal complexes using 4-(4-bromophenyl)-2,2'-bipyridine (BPBP) and their screening for antioxidant and lipoxygenase inhibition properties. 4-(4-bromophenyl)-[2,2'-bipyridine]-6-carboxylic acid was used as starting material and its decarboxylation resulted in BPBP. Decarboxylation by conventional heating method was compared with microwave decarboxylation method. Selected metal complexes of the ligand were synthesized with Ruthenium (II), Iron (II) and Cobalt (II) ions. The complexes were characterized using UV, IR, 1HNMR, ESI-MS and CHNS techniques. It was observed that BPBP acted as a bidentate ligand. The metal to ligand stoichiometry was 1:3 for all the synthesized complexes. The complexes had octahedral structure with C3 symmetry. The antioxidant activity was evaluated using free radical scavenging assay. BPBP showed insignificant antioxidant and lipoxygenase activities while its transition metal complexes showed promising activities. Antioxidant activity of Fe and Co-complexes was found significantly higher than the reference drug used in this study. [ABSTRACT FROM AUTHOR]

• Microwave-Assisted Organic Synthesis is a facile method for the synthesis of benzamide derivatives. • Benzamides of 2,6-dichloroaniline showed selective in vitro butyrylcholinesterase (BCHE) inhibitory activity. • 4-Bromosubstituted benzamide of 2,6-dichloroaniline (IC 50 value = 0.8 ± 0.6 µM) was the most active analogue. • Enzyme kinetic studies of synthesized compounds showed mixed as well as uncompetitive types of inhibition. A series of benzamide derivatives 1 – 12 with various functional groups (–H, –Br, –F, –OCH 3 , –OC 2 H 5 , and –NO 2) was synthesized using an economic, and facile Microwave-Assisted Organic Synthesis, and evaluated for acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) activity in vitro. Structure–activity relationship showed that the substitution of –Br group influenced the inhibitory activity against BCHE enzyme. Synthesized compounds were found to be selective inhibitors of BCHE. In addition, all compounds 1 – 12 were found to be non-cytotoxic, as compared to the standard cycloheximide (IC 50 = 0.8 ± 0.2 µM). Among them, compound 3 revealed the most potent BCHE inhibitory activity (IC 50 = 0.8 ± 0.6 µM) when compared with the standard galantamine hydrobromide (IC 50 = 40.83 ± 0.37 µM). Enzyme kinetic studies indicated that compounds 1 , 3 – 4 , and 7 – 8 showed a mixed mode of inhibition against BCHE, while compounds 2 , 5 – 6 and 9 exhibited an uncompetitive pattern of inhibition. Molecular docking studies further highlighted the interaction of these inhibitors with catalytically important amino acid residues, such as Glu197, Hip438, Phe329, and many others. [ABSTRACT FROM AUTHOR]

The carbazoles are synthesized from L-menthone and substituted phenyl hydrazines in acetic acid and show promising inhibitory activities against acetyl- and butyrylcholinesterase. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common cancer affecting women worldwide, including Pakistan. More than half of breast cancer patients have hormone-dependent breast cancer, which is developed due to the over-production of estrogen (the main hormone in breast cancer)., Method: The biosynthesis of estrogen is catalyzed by the aromatase enzyme, which thus serves as a target for the treatment of breast cancer. During the current study, biochemical, computational, and STD-NMR methods were employed to identify new aromatase inhibitors. A series of phenyl-3- butene-2-one derivatives 1-9 were synthesized and evaluated for human placental aromatase inhibitory activity. Among them, four compounds 2, 3, 4, and 8 showed a moderate to weak inhibitory activity (IC50 = 22.6 - 47.9 µM), as compared to standard aromatase inhibitory drugs, letrozole (IC50 = 0.0147 ± 1.45 µM), anastrozole (IC50 = 0.0094 ± 0.91 µM), and exemestane (IC50 = 0.2 ± 0.032 µM). Kinetic studies on two moderate inhibitors, 4 and 8, revealed a competitive- and mixed-type of inhibition, respectively., Result: Docking studies on all active compounds indicated their binding adjacent to the heme group and interaction with Met374, a critical residue of aromatase. STD-NMR further highlighted the interactions of these ligands with the aromatase enzyme., Conclusion: STD-NMR-based epitope mapping indicated close proximity of the alkyl chain followed by an aromatic ring with the receptor (aromatase). These compounds were also found to be non-cytotoxic against human fibroblast cells (BJ cells). Thus, the current study has identified new aromatase inhibitors (compounds 4, and 8) for further pre-clinical and clinical research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)