Bilgesu Onur Sucu

This study presents the synthesis of various non‐sulfonamide acyl hydrazone derivatives intended as multi‐target ligands for the treatment of Alzheimer's disease. The derivatives were thoroughly characterized using advanced spectroscopic techniques and their inhibitory activities against key enzymes, acetylcholinesterase (AChE) and human carbonic anhydrase I/II (hCA) were systematically assessed. The synthesized compounds demonstrated significant suppression of hCAs. The 4‐methoxycarbonyl compound ( 2a , Ki = 69.74 nM) exhibited a robust inhibitory effect against hCA I compared to the reference medication acetazolamide (AAZ, Ki = 373.46 nM). The 4‐dimethylamino compound ( 2b , K _i of 120.36 nM) exhibited superior potency compared to AAZ (K _i of 350.66 nM) against hCA II. 2,4‐dinitrobenzylidene ( 2n , K _i of 69.18 nM) derivative displayed a remarkable inhibitory effect against AChE compared to tacrine (THA, K _i of 205.78 nM). Additionally, in silico studies provided insight into the binding interactions enhancing the understanding of their multi‐target potential. This study identified compounds with varying affinities for hCA isoenzymes highlighting their potential as effective and selective hCA inhibitors. The reported compounds exhibited significant biological inhibitory potency indicating their potential as a promising lead compound against hCAs and AChE.

Novel imidazo[1,2‐ a ]pyridines bearing 1,2,3‐triazole moieties at the C3 position were synthesized. After the characterization of the synthesized compounds, their in vitro therapeutic activities were evaluated in various cancer cell lines (MCF7, A549, HePG2 and T98G). Methoxy substituted derivative was identified as the most potent compound based on the results of its anti‐proliferative activity on various cancer cell lines, as well as showing no cytotoxicity on the healthy human fibroblast cell line (MRC‐5). As an indicator of apoptosis, a significant decrease in the level of PARP protein was observed in the MCF7 cells treated with this derivative. Molecular docking studies were conducted on wide range of targets such as phosphoinositide 3‐kinase (PI3K), cyclin‐independent kinase 2 (CDK2), mitogen‐activated protein kinase (MEK), insulin‐like growth‐factor‐1 (IGF‐1), tubulin, DNA topoisomerase, poly (ADP‐ribose) polymerase (PARP) and B‐cell lymphoma‐2 (BCL2). All the compounds tested showed the lowest binding energies with target PARP1. Moreover, CDK2 and tubulin displayed relatively good binding scores. The docking poses and scores were cross‐checked with two different software and multiple protein conformations were included to incorporate flexible protein docking features. Finally, drug‐likeness properties of the compounds are further tested via Swiss‐ADME software.

This research focuses on the synthesis, characterization, and evaluation of the anti-cancer activity of novel 8-aryl substituted 1,3-diethylxanthine derivatives. The anti-proliferative activities of all the compounds were assessed using an MTT assay on four human cancer cell lines: breast cancer MCF7, human lung cancer A549, human brain cancers LN229, and U87. One of the derivatives of 1,3-diethylxanthine with a thiazole structure displayed strong anti-proliferative activity. 1,3-Diethyl-8-(thiazol-4-yl)-3,7-dihydro-1H-purine-2,6-dione (5) exhibited the strongest activity against A549, MCF7, LN229, and U87 cell lines, with IC50 values of 16.70, 78.06, 22.07, and 25.07 μM, respectively. Furthermore, the scratch assay was conducted to evaluate the effect of compound 5 on the inhibition of cell migration in A549 cells. The consistent results demonstrate that compound 5 exhibits potent anti-cancer activity, which could be further investigated to enhance its biological potential.

A series of novel 1,3,5‐trisubstituted‐1,2,4‐triazole derivatives were successfully synthesized from the starting materials of caffeic acid (CA) and ferulic acid (FA) in moderate to good yields (45–71 %). All novel compounds were screened for antiproliferative activity against three glioblastoma (GB) cell lines. Several compounds exhibited improved cytotoxic activities compared to the caffeic acid phenethyl ester (CAPE). Among the novel derivatives, 4‐(2‐(1‐benzyl‐3‐phenyl‐1 H ‐1,2,4‐triazol‐5‐yl)vinyl)‐2‐methoxyphenol ( 4) exhibited the most potent activity against the U87G, T98G and LN229 cell lines. Western blot results showed significantly reduced poly(ADP‐ribose) polymerase (PARP) and increased the Bcl‐2‐associated X (Bax) protein levels in T98G cells. Also, flow cytometry results using Annexin‐V/Propidium Iodide (PI) staining indicated that apoptosis was induced in T98G cells. It was found to be a promising drug candidate with strong physicochemical and bioavailability properties as a result of SwissADME calculations. These results show that novel compounds containing a 1,2,4‐triazole moiety have a good antiproliferative activity on GB cells.

Caffeic acid (CA), ferulic acid (FA) and caffeic acid phenethyl ester (CAPE) have a broad anticancer effect on various cell lines. In this study, nine ferulic and caffeic acid-based 1,2,4 and 1,3,4 oxadiazole molecular hybrids were synthesized and their cytotoxic activity was evaluated mainly against Glioblastoma (GBM) cell lines. Compounds 1 and 5 exhibited the highest inhibitory activity against three different GBM cell lines (LN229, T98G, and U87), without toxicity to healthy human mesenchymal stem cells (hMSC). In addition, their cytotoxicity was also evaluated against three additional cancer cell lines and more inhibitory results were found than GBM cell lines. The IC50 values of compound 5 in U87, T98G, LN229, SKOV3, MCF7, and A549 cells were determined as 35.1, 34.4, 37.9, 14.2, 30.9, and 18.3 μM. In the light of biological activity studies, the developed compounds have a high potential to lead studies for the development of new drug candidates for the treatment of cancer.

Leishmaniasis is a neglected parasitic disease that is widely seen in more than 60 countries worldwide, including Turkey and its subcontinental region. There are several chemotherapy agents for the treatment of leishmaniasis, including pentavalent antimonials—i.e., sodium stibogluconate (Pentostan) and meglumine antimoniate (Glucantim), pentamidine, conventional amphotericin B deoxycholate, miltefosine, paramomycin (aminosidine), and liposomal amphotericin B. However, these therapies are usually unsatisfactory due to dose-limiting toxicity issues and limited efficacy. Furthermore, resistance gained by parasites endangers future success of these therapies. Addressing these issues, the development of novel drugs with high efficacy has a vital importance. Latest studies have shown that bisnaphthalimidopropyl (BNIP) derivatives display high activity against Leishmaniasis parasites by selectively targeting parasitic sirtuin proteins and interacting with DNA. Despite the promising anti-parasitic activity, the low solubility and toxicity on human macrophages are the limitations to overcome. This study describes the new synthesis strategies for existing—i.e., BNIPDaoct and BNIPDanon—and novel BNIP derivatives differing in respect of their alkyl linker chain lengths. The new synthesis approach provides certain advantages compared to its existing alternatives reported in the literature. The proposed methodology does not only decrease the number of synthesis steps and production time of BNIPDaoct and BNIPDanon, but also provides higher yields, thereby making the synthesis highly cost-effective.