Synthesis of Purines by Inverse Electron Demand Diels-Alder Reactions of Amines with 1,3,5-Triazines and of Fluorinated Arenes by Palladium(0)-Catalyzed Cross-Coupling Reactions and Photophysical Properties of the Products

The formal inverse electron demand Diels-Alder reactions of amines with 1,3,5-triazine and 2,4,6-tris(trifluoromethyl)-1,3,5-triazine provided functionalized purines and bi-purines. Suzuki-Miyaura cross coupling reactions of different substituted mono-fluorobenzenes with different arylboronic acids afforded fluoro-substituted terphenyls with excellent site-selectivity. Sonogashira and Suzuki-Miyaura coupling reactions of 1,2-difluoro-, 1,3-difluoro-, and 1,4-difluoro-tetraiodobenzenes and of fluoro-pentaiodobenzene afforded alkynylated and arylated benzene derivatives. The fluorescence properties of benzene derivatives were studied.Die Diels-Alder-Reaktionen mit inversem Elektronenbedarf von Aminen mit 1,3,5-Triazin und 2,4,6-Tris(trifluoromethyl)-1,3,5-Triazin lieferte funktionalisierte Purine und Bipurine. Suzuki-Miyaura-Kreuzkupplungen von unterschiedlich substituierten Mono-Fluorobenzenen mit verschiedenen Boronsäuren lieferte fluorsubstituierte Terphenyle mit hervorragender Seitenselektivität. Sonogashira- und Suzuki-Miyaura-Kupplungsreaktionen von 1,2-Difluoro-, 1,3-Difluoro- und 1,4-Difluorotetraiodobenzen sowie 1-Fluoropentaiodobenzen ergaben die entsprechenden alkinylierten bzw. arylierten Produkte. Die Fluoreszenzeigenschaften vieler Benzenderivate wurden untersucht

Advances in Pharmacology of Isatin and its Derivatives: A Review

Isatin (1H-indole-2,3-dione), an indole derivative of plant origin, is involved in many pharmacological activities like antiallergic, antimalarial, antiviral and antimicrobial; isatin and its derivatives have been found to show promising results against various cancer cell lines. Isatin is a versatile precursor for many biologically active molecules and its diversified nature makes it a versatile substrate for further modifications. This review provides a brief overview on the recent advances and future perspectives on pharmacological aspects of isatin and its derivatives reported in the last decade.Keywords: Isatin, Anticancer, Antimicrobial, Monoamine oxidase, Antivira

Inhibitory mechanism against oxidative stress of caffeic acid

The purpose of this article is to summarize the reported antioxidant activities of a naturally abundant bioactive phenolic acid, caffeic acid (CA, 3,4-dihydroxycinnamic acid), so that new avenues for future research involving CA can be explored. CA is abundantly found in coffee, fruits, vegetables, oils, and tea. CA is among the most potential and abundantly found in nature, hydroxycinnamic acids with the potential of antioxidant behavior. Reactive oxygen species produced as a result of endogenous processes can lead to pathophysiological disturbances in the human body. Foods containing phenolic substances are a potential source for free radical scavenging; these chemicals are known as antioxidants. This review is focused on CA's structure, availability, and potential as an antioxidant along with its mode of action. A brief overview of the literature published about the prooxidant potential of caffeic acid as well as the future perspectives of caffeic acid research is described. CA can be effectively employed as a natural antioxidant in various food products such as oils

Imidazopyridine-Based Thiazole Derivatives as Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach

A new series of thiazole derivatives (4a-p) incorporating imidazopyridine moiety was synthesized and assessed for their in vitro potential α-glucosidase potency using acarbose as a reference drug. The obtained results suggested that compounds 4a (docking score = −13.45), 4g (docking score = −12.87), 4o (docking score = −12.15), and 4p (docking score = −11.25) remarkably showed superior activity against the targeted α-glucosidase enzyme, with IC50 values of 5.57 ± 3.45, 8.85 ± 2.18, 7.16 ± 1.40, and 10.48 ± 2.20, respectively. Upon further investigation of the binding mode of the interactions by the most active scaffolds with the α-glucosidase active sites, the docking analysis was accomplished in order to explore the active cavity of the α-glucosidase enzyme. The interpretation of the results showed clearly that scaffolds 4a and 4o emerged as the most potent α-glucosidase inhibitors, with promising excellent binding interactions with the active site of the α-glucosidase enzyme. Furthermore, utilizing a variety of spectroscopic methods, such as 1H-NMR, 13C-NMR, and HREI-MS, the precise structures of the synthesized scaffolds were determined

Synthesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities, and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows similar to 2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and similar to 1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of -12.9 kcal mol(-1) and -9.8 kcal mol(-1) respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be -10.1 kcal mol(-1) and -8.9 kcal mol(-1), respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver-Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer's disease. Moreover, compound (1) also exhibit better alpha-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds

Identification of novel oxadiazole-based benzothiazole derivatives as potent inhibitors of α-glucosidase and urease: Synthesis, in vitro bio-evaluation and their in silico molecular docking study

This research work represents a synthetic approach for the development of hybrids derivatives of oxadiazole-based benzothiazole (1–17) and diversity in derivatives was achieved using variety of aryl ring of S-substituted benzothiazole to see the effect on the biological activities. All the synthesized derivatives were evaluated for their in vitro α-glucosidase and urease inhibitory potential. The α-glucosidase and urease inhibition profile of the new derivatives represents moderate to good inhibitory potential with IC50 values ranging from 4.60 ± 1.20 µM to 48.40 ± 7.70 µM (α-glucosidase) and 8.90 ± 2.80 to 57.30 ± 7.70 µM (urease) respectively. The results were compared to standard acarbose (38.60 ± 4.50 µM) and thiourea (58.70 ± 6.80 µM) drugs respectively. Among the synthesized series, the analogs 1 having IC50 values of and 4.60 ± 1.20 (α-glucosidase), 8.90 ± 2.80 (urease) and 2 with IC50 values of 5.60 ± 1.60 (α-glucosidase) and 10.90 ± 2.10(urease) were found to be significantly active against targeted α-glucosidase and urease enzymes. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, 1H- and 13C- NMR spectroscopy. The molecular docking studies of the synthesized derivatives showed good correlations with the experimental findings. The binding modes of active compounds and their interactions with active site residues revealed them as possible anti-diabetics and anti-urease leads. The degree of activity and docking studies displayed by the novel innovative structural hybrids of oxadiazole-based benzothiazole moieties make these compounds new active leads and promising candidates for the development of anti-diabetics and anti-urease agents

Synthesis, in vitro analysis and molecular docking study of novel benzoxazole-based oxazole derivatives for the treatment of Alzheimer’s disease

Alzheimer's disease (AD) is treated by targeting cholinesterase enzymes like acetylcholinesterase and butyrylcholinesterase, and these enzymes' inhibitors serve as important tools for treatment of alzheimer diseases. Hybrid analogues with a 1,3-oxazole moiety based on benzoxazole were designed, developed, and then tested for their cholinesterase inhibition. All the newly synthesized analogues showed moderate to good inhibitory potentials having IC50 values raging between 0.90 ± 0.05 µM to 35.20 ± 0.70 µM against acetylcholinesterase and 1.10 ± 0.10 µM to 37.70 ± 0.60 µM against butyrylcholinesterase enzymes. Among the series, the analogue 11 (IC50 = 0.90 ± 0.05 µM), (IC50 = 1.10 ± 0.10 µM) and 18 (IC50 = 1.20 ± 0.05 µM), (IC50 = 2.10 ± 0.10 µM) being the strongest acetylcholinesterase and butyrylcholinesterase inhibitors as compared to standard donepezil drug. Nonetheless, the remaining analogues also displayed better inhibition profile against both these targeted enzymes. Furthermore, the structures of all the synthesized analogues were confirmed by using HREI-MS, 1HNMR and 13CNMR spectroscopy. Additionally, molecular docking experiments were conducted to determine the potential mode of interaction between the majority of active analogues and the enzyme active site. The findings corroborated the experimental data

Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives

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