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In this study, 2′,4′,6′-Trimethoxyacetophenone was reacted with various fluorine-substituted benzaldehydes in the presence of an aqueous solution of 50%-potassium hydroxide, and new chalcone derivatives in the structure of 1,3-diaryl-2-propenone comprising both fluorine and methoxy groups in the aromatic B ring were obtained in high yields under mild conditions. In base-catalyzed Claisen-Schmidt condensations, MeOH is usually used as solvent. In the condensation reactions performed with mono-fluorine-substituted benzaldehydes in MeOH, the corresponding fluorine-substituted chalcone derivatives in the B ring were synthesized in high yield. On the other hand, when di- and tri-fluorine-substituted benzaldehydes were used, it was determined that a nucleophilic aromatic substitution (SNAr) occurred in the reaction condition and the condensation yield decreased. Consequently, fluorine-methoxy substituted chalcone derivatives were isolated by substitution of fluorine and methoxy group in para position in the aromatic B ring. On the other hand, it was found that when THF was used as the reaction solvent, chalcone derivatives carrying only fluorine atoms could be obtained with excellent chemical selectivity without any competitive aromatic nucleophilic substitution (SNAr) in the condition. Particularly in the synthesis studies of such fluorine-substituted chalcones, it was determined that the Claisen–Schmidt condensation ratio is dependent on the effect of the solvent in addition to steric and electronic factors.

Enzyme inhibition is a very active area of research in drug design and development. Chalcone derivatives have a broad enzyme inhibitory activity and function as potential molecules in the development of new drugs. In this study, the synthesized novel halogenated chalcones with bromobenzyl and methoxyphenyl moieties were evaluated toward the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and human erythrocyte carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes. They showed highly potent inhibition ability toward AChE with Ki values of 1.83 +/- 0.21-11.19 +/- 0.96 nM and BChE with Ki values of 3.35 +/- 0.91-26.70 +/- 4.26 nM; hCA I with Ki values of 29.41 & PLUSMN; 3.14-57.63 & PLUSMN; 4.95 nM, and hCA II with Ki values of 24.00 & PLUSMN; 5.39-54.74 & PLUSMN; 1.65 nM. Among the tested enzyme inhibitions, compounds 14 and 13 were the most active compounds against AChE and BChE. Docking studies were performed to the most active compounds against AChE, BChE, hCA I and hCA II to propose a binding mode in the active site and molecular dynamics simulations were studied to check the molecular interactions and the stability of the ligands in the active site. The results may contribute to the development of new drugs particularly to treat some global disorders including Alzheimer's disease (AD), glaucoma, and diabetes., Erzincan Binali Yildirim University [TSA-2017-495], Acknowledgements We thank to the Erzincan Binali Yildirim University (Grant Number: TSA-2017-495) provide financial support.

Aims Flavonoids and related compounds, such as quercetin‐based antiviral drug Gene‐Eden‐VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS‐CoV proteases. In this study, we aimed to compare the anti‐SARS CoV‐2 activities of both newly synthesized chalcone derivatives and these two drugs. Methods Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS‐CoV‐2 by calculating the RT‐PCR cycling threshold (Ct ) values. Results Antiviral activities of the compounds varied because of being dose dependent. Compound 6, 7, 9, and 16 were highly effective against SARS‐CoV‐2 at the concentration of 1.60 µg/mL. Structure‐based virtual screening was carried out against the most important druggable SARS‐CoV‐2 targets, viral RNA‐dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti‐coronavirus disease‐2019 drug candidates. Conclusions Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from −4.370 to −2.748 kcal/mol along with their toxicological, ADME, and drug‐like properties.

In this study, we report the synthesis of novel tris-chalcones and testing of human carbonic anhydrase I, and II isoenzymes (hCA I, and hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glycosidase (alpha-Gly) inhibitors for the development of novel chalcone structures towards for treatment of some diseases. The compounds demonstrated K-i values between 13.6 +/- 1.1 and 50.0 +/- 17.1 nM on hCA I, 9.9 +/- 0.8 and 39.5 +/- 15.1 nM on hCA II, 3.1 +/- 0.2 and 20.1 +/- 1.9 nM on AChE, 4.9 +/- 0.4 and 14.7 +/- 5.2 nM on BChE and 3.9 +/- 0.2 and 22.4 +/- 10.7 nM on alpha-Gly enzymes. The results revealed that novel tris-chalcones can have promising drug potential for glaucoma, leukaemia, epilepsy; Alzheimer's disease that was associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes., Erzincan Binali Yildirim University [TSA-2017-495], This work was supported by the research funds from Erzincan Binali Yildirim University [Grant Number: TSA-2017-495].

Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus (SARS-CoV-2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS-CoV proteases. Hydroxychloroquine and Favipiravir have been used in many countries since the beginning of the pandemic with the thought that they may have antiviral activity against SARS CoV-2. In this study, we aimed to compare the anti-SARS CoV-2 activities of both newly synthesized chalcone derivatives and these two drugs.The current study aimed to determine the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (Ct) values. Antiviral activities of the compounds varied due to being dose dependent. Compound 6, 7, 9 and 16 were highly effective against SARS-CoV-2 at concentrations of 1.60 µg/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase (RdRp), to identify putative inhibitors that could facilitate the development of potential anti-COVID-19 drug candidates. Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from − 4,370 to -2,748 kcal/mol along with their toxicological, ADME, and drug-like properties.

Antimetabolites, which are metabolic antagonists used in the treatment of cancer and viral diseases by replacing metabolites, inhibit the action of metabolic enzymes and disrupt the pathways of synthesis of structural units necessary for the formation of nucleic acids. Purine antagonists, that are subunits of antimetabolites, reduce the production of purine bases, and hence, cause the nucleotide production to stop and bring about the death of cancer cells. Fludarabine (2-fluoro-ara-AMP), which is used in chemotherapy, is an antimetabolite of the purine class containing mono phosphate in its structure. In this study, a protocol was presented to effectively and efficiently synthesis of 6-(4-phenylpiperazine-1-yl)-9-(β-D-ribofuranosyl)-9H-purine-5'- O-phosphate compound in six steps and 25% overall yield starting with commercially available 6-chloropurine.

A novel class of fluoro-substituted tris-chalcones derivatives (5a-5i) was synthesized from phloroglucinol and corresponding benzaldehydes. A three step synthesis method was followed for the production of these trischalcone compounds. The structures of the newly synthesized compounds (5a-5i) were confirmed on the basis of IR, H-1 NMR, C-13 NMR, and elemental analysis. The compounds' inhibitory activities were tested against human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glycosidase (alpha-Gly). These chalcone derivatives had K, values in the range of 19.58-78.73 nM for hCA I, 12.23-41.70 nM for hCA II, 1.09-6.84 nM for AChE, 8.30-32.30 nM for BChE and 0.93 +/- 0.20-18.53 +/- 5.06 nM against alpha-glycosidase. These results strongly support the promising nature of the tris-chalcone scaffold as selective carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and aglycosidase inhibitor. Overall, due to these derivatives' inhibitory potential on the tested enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, leukemia, epilepsy; Alzheimer's disease; type-2 diabetes mellitus that are associated with high enzymatic activity of carbonic anhydrase, acetylcholine esterase, butyrylcholinesterase, and alpha-glycosidase., Erzincan Binali Yildirim University [TSA-2017-495], We thank to the Erzincan Binali Yildirim University (Grant Number: TSA-2017-495) provide financial support.

N,O problem: An asymmetric catalytic one‐pot N,O‐ and O,O‐acetalization cascade is presented. This strategy is based on catalytic asymmetric conjugate addition and subsequent acid‐catalyzed acetal formation that allows efficient and fast construction of functionalized dioxabicyclo‐ and oxaazabicyclo[3.3.1]nonane structures that are important motifs in several natural products and pharmaceutically interesting compounds.

Treatment of the cyclic nitrile (I) with allylic alcohols and subsequent thermolysis allows new access to cyclic quaternary oxonitriles.

Quaternary oxonitriles are stereoselectively generated from the union of five-, six-, and seven-membered 2-chloroalkenecarbonitriles with chiral alcohols via a Claisen rearrangement. The strategy rests on a new conjugate addition-elimination of allylic alkoxides to 2-chlorocycloalkenecarbonitriles to afford substituted 2-alkoxyalkenenitriles. Subsequent thermolysis unmasks a cyclic oxonitrile while selectively forming a new quaternary center with enantiomeric ratios typically greater than 9:1. The overall alkylation strategy addresses the challenge of enantioselectively generating hindered, quaternary centers while simultaneously installing ketone, nitrile, and olefin functionalities., TUBITAK (106T100)

A new and simple method for the synthesis of the primary allyl chlorides and bromides 9–16 from the secondary or tertiary allyl alcohols 3–8 and acyl halide was developed (Scheme 2, Table 1). Non-commercially available secondary and tertiary allyl alcohols were synthesized from the related ketones and aldehydes via the addition of vinylmagnesium chloride. Mechanistic studies indicate that the alcohols were first acetylated by the acetyl halide and then protonated prior to substitution by the halide, Cl− or Br−, via an SN2′ reaction, to yield the primary halides (Scheme 5).

A new and simple method for the synthesis of the primary allyl chlorides and bromides 9–16 from the secondary or tertiary allyl alcohols 3–8 and acyl halide was developed (Scheme 2, Table 1). Non-commercially available secondary and tertiary allyl alcohols were synthesized from the related ketones and aldehydes via the addition of vinylmagnesium chloride. Mechanistic studies indicate that the alcohols were first acetylated by the acetyl halide and then protonated prior to substitution by the halide, Cl− or Br−, via an SN2′ reaction, to yield the primary halides (Scheme 5).