ABSTRACT
A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64-70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives' significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development.
ABSTRACT
Terpyridine-based metal complexes have emerged as versatile and indispensable building blocks in the realm of modern chemistry, offering a plethora of applications spanning from materials science to catalysis and beyond. This comprehensive review article delves into the multifaceted world of terpyridine complexes, presenting an overview of their synthesis, structural diversity, and coordination chemistry principles. Focusing on their diverse functionalities, we explore their pivotal roles in catalysis, supramolecular chemistry, luminescent materials, and nanoscience. Furthermore, we highlight the burgeoning applications of terpyridine complexes in sustainable energy technologies, biomimetic systems, and medicinal chemistry, underscoring their remarkable adaptability to address pressing challenges in these fields. By elucidating the pivotal role of terpyridine complexes as versatile building blocks, this review provides valuable insights into their current state-of-the-art applications and future potential, thus inspiring continued innovation and exploration in this exciting area of research.
ABSTRACT
A library of 16 3-benzyl-N 1-substituted quinoxalin-2-ones was synthesized as N 1-substituted quinoxalines and quinoxaline-triazole hybrids via click reaction. These compounds were tested for their anticancer activity via MTT assay on HCT-116 and normal colonocyte cell lines to assess their cytotoxic potentials and safety profiles. Overall, compounds 6, 9, 14, and 20 were found to be promising anticolorectal cancer agents; they exhibited remarkable cytotoxicity (IC50 0.05-0.07 µM) against HCT-116 cells within their safe doses (EC100) on normal colon cells. Their pronounced anticancer activities were observed as severe morphological alterations and shrinkage of the treated cancer cells. Besides, qRT-PCR analysis was conducted showing the potential of the promising hits to downregulate HIF-1a, VEGF, and BCL-2 as well as their ability to enhance the expression of proapoptotic genes p21, p53, and BAX in HCT-116 cells. In silico prediction revealed that most of our compounds agree with Lipinski and Veber parameters of rules, in addition to remarkable medicinal chemistry and drug-likeness parameters with no CNS side effects. Interestingly, docking studies of the compounds in the VEGFR-2' active site showed significant affinity toward the essential amino acids, which supported the biological results.
ABSTRACT
In the current study, a series of fluorine-substituted piperidine derivatives (1-8) has been synthesized and characterized by various spectroscopic techniques. In vitro and in vivo enzyme inhibitory studies were conducted to elucidate the efficacy of these compounds, shedding light on their potential therapeutic applications. To the best of our knowledge, for the first time, these heterocyclic structures have been investigated against α-glucosidase and cholinesterase enzymes. The antioxidant activity of the synthesized compounds was also assessed. Evaluation of synthesized compounds revealed notable inhibitory effects on α-glucosidase and cholinesterases. Remarkably, the target compounds (1-8) exhibited extraordinary α-glucosidase inhibitory activity as compared to the standard acarbose by several-fold. Subsequently, the potential antidiabetic effects of compounds 2, 4, 5, and 6 were validated using a STZ-induced diabetic rat model. Kinetic studies were also performed to understand the mechanism of inhibition, while structure-activity relationship analyses provided valuable insights into the structural features governing enzyme inhibition. Kinetic investigations revealed that compound 4 displayed a competitive mode of inhibition against α-glucosidase, whereas compound 2 demonstrated mixed-type behavior against AChE. To delve deeper into the binding interactions between the synthesized compounds and their respective enzyme targets, molecular docking studies were conducted. Overall, our findings highlight the promising potential of these densely substituted piperidines as multifunctional agents for the treatment of diseases associated with dysregulated glucose metabolism and cholinergic dysfunction.
