Industrial production of amoxicillin trihydrate (AMCT) often suffers from low yield, impurity inclusion, and inconsistent crystal morphology. This study introduces a scalable green crystallization strategy using malic acid as a biodegradable habit modifier, developed as part of an improved eco-friendly AMCT manufacturing framework. A hybrid optimization approach integrating Taguchi design with Artificial Neural Network (ANN) modeling was employed to capture both linear and nonlinear interactions among critical process variables. Multi-technique characterization (XRD, FTIR, DSC, BET, LC-MS) confirmed that malic acid preserves lattice integrity while substantially refining particle attributes, reducing crystallite size from 85.9 to 66.4 nm and increasing specific surface area from 5.27 to 11.07 m(2) g(-1). This significant increase in surface area is a key physical factor theoretically favoring improved dissolution kinetics. The ANN model exhibited excellent predictive performance (R-2 > 0.99) for both purity and yield. Under optimized conditions (2.5 M malic acid, pH 5.5, 60 min, 1500 rpm), AMCT crystals were obtained with 99.21% purity and 61.82% yield. These results demonstrate a robust, data-driven framework for sustainable AMCT production, providing a high-performance alternative to conventional mineral-acid-based crystallization methods.

Breast cancer is one of the leading cancer types in terms of morbidity and mortality worldwide. Although developing technology, early diagnosis and treatment opportunities provide positive contributions to the treatment of breast cancer, research on new drugs that are less toxic to healthy cells, safer and more effective for cancer cells, increasing the quality of life of the patient is still ongoing. Coumarin and its derivatives have been shown great interest to develop safer and more effective anticancer drugs. Therefore, we investigated the anticancer activity of novel coumarin-3-carboxamide derivative 3i in MDA-MB-231 cells. We found that coumarin-3-carboxamide derivative 3i inhibited cell proliferation, colony formation and migration. However, coumarin-3-carboxamide derivative 3i did not induce apoptosis and autophagy. Consequently, our findings suggest for the first time that novel coumarin-3-carboxamide 3i has anticancer activity and may be an important drug candidate for the treatment of triple-negative breast cancer. Further investigations are required to elucidate its impact on breast cancer.

This study investigates the role of malic acid, a natural and environmentally friendly acid, in optimizing the crystallization process of amoxicillin trihydrate (AMCT). For the first time, the effects of malic acid on AMCT purity and yield were systematically analyzed and visualized using an Ishikawa diagram to elucidate complex interactions. Full factorial design and multiple response optimization were employed, with experiments conducted using Minitab V19 software. The results demonstrated that malic acid concentration, crystallization time, pH, and stirring speed significantly influence the purity and yield of AMCT crystals. The optimal conditions—2.5 M malic acid, pH 5.5, stirring speed of 1000 rpm, and crystallization time of 60 min—produced crystals with 99.21% purity and 62.6% yield. A comparative analysis with citric acid, previously studied by our group, highlighted malic acid's advantages, including improved yield and balanced purity. This research emphasizes the potential of organic acids as sustainable alternatives in pharmaceutical crystallization, offering insights into eco‐friendly production methods. The findings contribute to industrial applications by promoting green chemistry principles and advancing environmentally conscious pharmaceutical practices.

In this study, thirteen simple coumarin derivatives were evaluated for antibacterial and antifungal activities. The test results showed that the coumarin derivatives used, especially the 8, 11, 12 and 13 derivatives, were more susceptible to gram positive bacteria. Furthermore, the antifungal activity of compound 11 was observed to be promising. Insertion analyzes were applied to elucidate the interaction mechanisms between coumarin compounds and target proteins (selected from S. aureus and C. albicans). Compound 11 exhibited high binding affinity for CYP51 (-7.32 kcal/mol) and strong protein-ligand molecular interactions. As a result, it is stated that 11 is open to various chemical modifications and has a good initial skeletal molecular structure for antifungal compound designs.

In this study, a total of 12 coumarin-chalcone derivatives, 6 of which are original were synthesized. The structures of the newly synthesized compounds were elucidated by H-1 NMR, C-13 NMR, IR, and elemental analysis methods (7g-7l). The antioxidant potencies measured by using CUPRAC method (Trolox equivalent total anti-oxidant capacity) were as follows: 7j > 7i > 7c > 7d > 7k > 7l > 7f > 7h > 7e > 7g > 7a > 7b. Furthermore, the compounds were evaluated against human carbonic anhydrases I, II, acetylcholinesterase and alpha-glycosidase enzymes. Compounds 7c, 7e, 7g, 7i, 7j and 7l showed promising human carbonic anhydrase I inhibition compared to the standard Acetazolamide (K-i: 16.64 +/- 4.72-49.82 +/- 5.82 nM vs K-i: 57.64 +/- 5.41 nM). In addition, all compounds exhibited strong inhibition against acetylcholinesterase and a-glycosidase. K-i values were between 2.39 +/- 0.97-9.35 +/- 3.95 nM (Tacrine K-i: 13.78 +/- 4.36 nM) for acetylcholinesterase, and 14.49 +/- 8.51-75.67 +/- 26.38 nM (Acarbose K-i: 12600 +/- 78.00 nM) for a-glycosidase. Binding of 7g was predicted using molecular docking and stability of the complex was confirmed with molecular dynamics simulations which shed a light on the observed activity against acetylcholinesterase. Finally, cyclic voltammetry was also used for the electrochemical characterization of the synthesized compounds.

One of the important reactions to obtain a new carbon-carbon bond is the Stetter reaction, which is generally via a nucleophilic catalyst like cyanide or thiazolium-NHC catalysts. In particular, 1,4-diketones with very functional properties are obtained by the Stetter reaction with the intermolecular reaction of an aldehyde and an α,β-unsaturated ketone. In this study, we synthesized new derivatives (substituted arenoxy) of 1,4-diketone compounds (2a-2n) with useful features by a new version of the Stetter reaction method. In our work, arenoxy benzaldehyde derivatives with different structures as the Michael donor and methyl vinyl ketone as the Michael acceptor were used for the intermolecular Stetter reaction. The reaction was catalyzed by 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (3b), using triethylamine for the basic medium and dimethyl sulfoxide as the solvent. As a result, some novel arenoxy-substituted 1,4-diketones were gained with good yields at room temperature within 24 h through an intermolecular Stetter reaction. In addition, new furan and pyrrole derivatives were prepared by performing the cyclization reaction with one of the obtained new diketone compounds.

Lead molecules containing 1,4-quinone moiety are intriguing novel compounds that can be utilized to treat cancer owing to their antiproliferative activities. Nine previously reported quinolinequinones (AQQ1-9) were studied to better understand their inhibitory profile to produce potent and possibly safe lead molecules. The National Cancer Institute (NCI) of Bethesda chose all quinolinequinones (AQQ1-9) based on the NCI Developmental Therapeutics Program and tested them against a panel of 60 cancer cell lines. At a single dose and five further doses, AQQ7 significantly inhibited the proliferation of all leukemia cell lines and some breast cancer cell lines. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ7, in MCF7 and T-47D breast cancer cells, DU-145 prostate cancer cells, HCT-116 and COLO 205 colon cancer cell lines, and HaCaT human keratinocytes using the MTT assay. AQQ7 showed particularly high cytotoxicity against MCF7 cells. Further analysis showed that AQQ7 exhibits anticancer activity through the induction of apoptosis without causing cell cycle arrest or oxidative stress. Molecular docking simulations for AQQ2 and AQQ7 were conducted against the COX, PTEN, and EGFR proteins, which are commonly overexpressed in breast, cervical, and prostate cancers. The in vitro ADME and in vivo PK profiling of these compounds have also been reported.

It is quite challenging to find out bioactive molecules in the vast chemical universe. Quinone moiety is a unique structure with a variety of biological properties, particularly in the treatment of cancer. In an effort to develop potent and secure antiproliferative lead compounds, five quinolinequinones (AQQ1-5) described previously have been selected and submitted to the National Cancer Institute (NCI) of Bethesda to envisage their antiproliferative profile based on the NCI Developmental Therapeutics Program. According to the preliminary in vitro single-dose anticancer screening, four of five quinolinequinones (AQQ2-5) were selected for five-dose screening and they displayed promising antiproliferative effects against several cancer types. All AQQs showed a excellent anticancer profile with low micromolar GI50 and TGI values against all leukemia cell lines, some non-small cell lung and ovarian cancer, most colon, melanoma, and renal cancer, and in addition to some breast cancer cell lines. AQQ2-5 reduced the proliferation of all leukemia cell lines at a single dose and five additional doses, as well as some non-small cell lung and ovarian cancer, the majority of colon cancer, melanoma and renal cancer, and some breast cancer cell lines. This motivated us to use in vitro, in silico, and in vivo technologies to further investigate their mode of action. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ3, in HCT-116 colon cancer, MCF7 and T-47D breast cancer, and DU-145 prostate cancer cell lines, and HaCaT human keratinocytes. Concomitantly, IC50 values of AQQ2 and AAQ3 against MCF7 and T-47D cell lines of breast cancer, DU-145 cell lines of prostate cancer, HCT-116 cell lines of colon cancer, and HaCaT human keratinocytes were determined. AQQ2 exhibited anticancer activity through the induction of apoptosis and caused alterations in the cell cycle. In silico pharmacokinetic studies of all analogs have been carried out against ATR, CHK1, WEE1, CDK1, and CDK2. In addition to this, in vitro ADME and in vivo pharmacokinetic profiling for the most effective AAQ (AAQ2) have been studied.

This study investigates the use of environmentally friendly citric acid as the main player in the process, rather than as an additive, to remove impurities from amoxicillin trihydrate (AMCT) crystals, aiming to optimize their purity and yield. By manipulating the concentration of citric acid, mixing speed, crystallization time, and pH, the researchers conducted experiments using a full factorial design. The dissolution stage was analyzed in both batch and continuous crystallization processes, emphasizing the significance of citric acid in enhancing crystallization. HPLC analyses were performed on the resulting crystals, and the data were analyzed using the Multi-Vari Chart program. The findings demonstrated that higher citric acid concentrations positively affected the yield, while factors such as crystallization time, mixing speed, and pH also contributed to the increased yield. The crystals obtained exhibited desirable dimensions sought after in the pharmaceutical industry, eliminating the need for additional purification steps. This study showcased the potential of citric acid in AMCT crystallization, offering advantages in product design, purification, and synthesis. The optimized conditions included a citric acid concentration of 2.0 M, mixing speed of 1000 rpm, crystallization time of 120 min, and pH of 5.5. Notably, the developed process proved to be environmentally friendly by avoiding the use of harmful chemicals, serving as a green alternative for crystallization processes, and producing purer AMCT products. Overall, this research contributes to the existing literature by highlighting the efficacy of citric acid in impurity removal and the optimization of AMCT crystal purity and yield.

In this paper, Epilobium angustifolium L. in Turkey was investigated for total phenolics, flavonoids, and anthocyanin amounts. Furthermore, the ethanol extract of the leafs was evaluated for antioxidant activities as ABTS, hydroxyl radical scavenging, superoxide radical scavenging, power of reduction, and bleaching of beta-carotene. The total phenolic and flavonoid contents of the ethanolic extract were found to be 468,11± 1,53 micrograms of pyrocatechol per milligram of the extract and 103,05 ± 2,36 µg catechin per milligram of the extract, respectively. As the extract concentration increased, the amount of anthocyanins showed a decrease (17.92±8.08 and 13.56±8.22 for the 1 mg/mL and 2 mg/mL concentrations, respectively). In the β-carotene bleaching test, higher activity was observed than BHA ( 1.540±0.053 and 1, respectively). The results of the reduction power, hydroxyl radical scavenging, and ABTS tests gave either very close values or higher than the standards chosen. Superoxide radical scavenging activity gave a lower value than the Trolox selected as standard. Antioxidant activity of ethanol extract was found to be 94.22±0.05958 (ABTS), 78.77±0.84099 (hydroxyl radical scavenging) and 47.86±0.03915 (superoxide radical scavenging). The experimental data indicate that Turkey Epilobium angustifolium L. ethanol extract can be used pharmacologically.

This study provides an enzymatic kinetic resolution (EKR) method for the biocatalytic enantioselective synthesis of chiral beta-keto acetates. For the first time, the attitude of several lipase enzymes has been examined under different conditions for the EKR of the racemic 1,3-keto alcohols. We found that the Amano lipase fromPseudomonas fluorescens(AL-PF) lipase showed the best results for the resolution of the racemic 1,3-keto alcohols. We developed a highly effective EKR method by changing the enzyme, temperature, solvent, and enzyme amount in order to synthesize the chiral 1,3-keto esters, which are useful intermediates in organic synthesis. This study presents an efficient method for the synthesis of 1,3-keto acetates with a good yield and high enantioselectivity with theRconfiguration.

This study was initiated by 7-hydroxy-4-methylcoumarin 1 synthesis according to the Peckmann reaction with resorcinol and ethylacetoacetate. This compound was converted into 8-formyl-7-hydroxy -4-methylcoumarin 2 compound by the Duff reaction. This aldehyde obtained was reacted with 6-amino-1,4-benzodioxane and 2-amino benzamide, which have their specific biological activities, to synthesize the original two novel compounds. While 3 (7-Hydroxy-4-methyl-8-[(2,3-dihidro-1,4-benzodioxin-6-yl)iminomethyl]-2H-1-benzopiran-2-on) is obtained as a coumarin schiff base, ring closure was observed at 4 (2-(2’-Hydoxy-5-methyl coumarin-1-yl)-2,3-dihidro quinazoline-4(1H)-on). Our compounds are thought to exhibit biological activity. Their structures were identified by IR, 1H NMR, 13C NMR , MS analysis.

In this study; Numerous coumarin compounds were synthesized by Pechmann and Knoevenagel methods, and the substitution of the formyl group was provided by the Duff reaction. The IR spectras and melting points of the synthesized compounds were compared with the literature values. Also confirmed by GC/MS analysis. And the synthesized coumarin derivatives were compared in terms of antioxidant activity according to DPPH and Cuprac methods. The main aim of the study is to determine the effects of substituents on antioxidant activity.

Novel chiral gamma- and delta- amino esters 2 a-k were synthesized by enantioselective reduction of N-aryl gamma- and delta-imino esters with aryl, substituted aryl, and heteroaryl groups 1 a-k using trichlorosilane activated with optically active N-pivaloyl L-proline I in high yields (50%-98%) with enantioselectivities (10%-84% enantiomeric excess). The structures of the chiral amino esters 2 a-k were clarified by infrared, nuclear magnetic resonance (H-1 and C-13) and gas chromatography-mass spectrometry. The enantiomeric excess of these compounds were identified by chiral high-performance liquid chromatography using a Chiralpak AD-H column. The highest ee of 84% and highest yield of 98% were found for 2 d.

This study was undertaken to examine the possible cytotoxic effect of anilide and semicarbazone derivatives of (4-12) monoketo eicosanoic acids (3.125 – 100 µM) on canine mammary tumour cell line (CMT-U27) as compared with doxorubicin. Among these compounds, 8-semicarbazone eicosanoic acid (3) and 10-keto eicosanoic acid anilide (9) displayed effective cytotoxic potential against CMT-U27 and IC50 concentrations were recorded at 1.952 µM and 54.00 µM, respectively.

4-Methyl-8-formyl- and 4-phenyl-8-formyl coumarins have been synthesized by Pechmann reaction using oxalic acid catalyst for the first time. 4-Propyl-7-hydroxy-, and 4-methyl-7-methoxy coumarins have also been accomplished by this catalyst for the first time. They have been characterizated by IR, H-1-NMR, C-13-NMR, mass and elemental analysis. Furthermore, the obtained coumarins were compared according to antioxidant activity by DPPH method.

In this study, it is aimed to investigate the chemical composition of the essential oils, antioxidant activity, and polyphenol content of methanol extracts of M.comminus L. leaves and berries. M.comminus L. Plant was collected from Yalova, Marmara region of Turkey. Its essential oil was prepared by hydrodistillation in a Clevenger-type apparatus in 0.5%. The chemical composition of the essential oil was analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC–MS), using two columns with stationary phases of different polarity (polar ZB-WaxMS/apolar ZB-5MS). On both columns monoterpenes were determined to be the dominant compounds. The myrtenyl acetate, α-pinene, 1,8-cineole, linalool, and limonene were the remarkable substances. As polyphenol compounds, the flavanoids and anthocyanidins in leaves and berries were detected by HPLC and furthermore, their antioxidant activities were studied with DPPH, Cuprac and Folin – Ciocalteu method of the methanolic extracts.

A series of some 3-13 monohydroxy eicosanoic acid isomers were evaluated for their antielastase, antiurease and antioxidant activities for the first time in this study. All the test compounds exhibited antielastase, antiurease and antioxidant activities. According to the obtained results the hydroxy eicosanoic acid isomers locating in the middle and close to the middle of the chain showed higher antielastase, antiurease and antioxidant activities rather than that of the other isomers. Therefore, 3-13 monohydroxy eicosanoic acid isomers can be used in agriculture, pharmacy and cosmetic industries due to their excellent antielastase, antiurease and antioxidant activities.

Herein, β-hydroxy methyl esters with an even carbon chain length of 12–20 1b–5b were synthesized by three different asymmetric reduction methods I, II III from their corresponding β-keto methyl esters 1a–5a with the aim of determining their elastase activities. In method I, chiral catalyst A was prepared from chiral ligand (R)-binaphthol 1, while in method II, chiral catalyst B was synthesized from (2R,3R)-diisopropyl tartrate 2. Chiral catalyst B has not previously been used in asymmetric borane reductions or in the asymmetric synthesis of chiral β-hydroxy methyl esters. In method III, an asymmetric reduction was catalysed by (R)-Me-CBS oxazaborolidine 3. Hydride transfer was carried out in all of these methods by BH3·SMe2. Chiral hydroxy methyl esters with an (S)-configuration were synthesized by method I and with an (R)-configuration via methods II and III. The chiral hydroxy methyl esters obtained were analysed by chiral HPLC for their ee % values. Methods I, II and III were applied to long chain β-keto methyl esters for the first time. The reduction methods I, II and III were examined in terms of reaction yield and enantiomeric excess according to carbon chain length and the variable ratio of chiral catalysts to β-keto methyl ester. The highest enantiomeric excess of 90% ee was found in method III for 12 and 14 carbon numbers.