Synthesis of New C-C Linked Bichalcones and Their Antimicrobial and Antioxidant Activities

Bichalcones are obtained naturally from the genus Rhus. Bichalcones have attracted attention not only from a synthetic perspective but also because of their broad-spectrum biological activities. A series of methoxy-substituted chalcones (1–9) yielded C-C linked bichalcones (10–18) by the Ullmann coupling method, and their antimicrobial and antioxidant activities were assessed in this study. The confirmation of the synthesized compounds\u27 structures was performed by NMR (1H, 13C, APT, and COSY), FT-IR, UV, and HRESI-TOF-MS data. According to the preliminary results, a number of the said compounds exhibited an interesting activity against Candida tropicalis. Moreover, the antioxidant activities of bichalcones (10–18) were evaluated according to DPPH and FRAP methods. Concerning antioxidant activities, compounds 15 and 16 were the most active compared to Trolox used as a standard. Of all the synthesized new bichalcone derivatives, compounds 10, 11, 12, 14, and 17 displayed higher activity against to fungal microorganism Candida tropicalis. Compounds 15 and 16 were found to have the highest antioxidant activity according to both DPPH and FRAP methods

Biological evaluation and synthesis of new pyrimidine-2(1H)-ol/-thiol derivatives derived from chalcones using the solid phase microwave method

Alpay Karaoglu, Sengul/0000-0003-1047-8350; YUCEL, TAYYIBE BEYZA/0000-0002-2632-8325WOS: 000431245300026Twenty-five new hydroxy- and methoxy-substituted 4,6-diarylpyrimidin-2(1H)-ol (20-34) and 4,6-diarylpyrimidine-2(1H)-thiol derivatives (35-44) were synthesized from the reaction of the corresponding 1,3-diaryl-2-propene-1-one compounds (1-19) with urea or thiourea using the solid-phase microwave method. All the new synthetic compounds (20-44) were evaluated with regard to their \g=a\-glucosidase activity. However, only compounds 22-25, 27, 31, 34, 35, 37, and 40 exhibited a greater inhibitory effect than standard acarbose. The IC50 values of the active compounds ranged between 2.36 and 13.34 mu M. The 25 new compounds were also screened for their in vitro pancreatic lipase activity and compounds 20-27 and 35-39 were found to be active. Of these compounds 26, 27, and 39 exhibited the best antilipase activities at concentrations of 0.40 +/- 0.06, 0.26 +/- 0.07, and 0.29 +/- 0.026 mu M. All the new compounds (20-44) were evaluated for their in vitro antimicrobial activity for nine test microorganisms. Compounds 20-24 and 35-39 were determined to possess a significant broad spectrum against the gram-positive bacteria Escherichia faecalis, Staphylococcus aureus, and Bacillus cereus among the tested bacterial agents. Compounds 20-24 and 35-39 exhibit the best activity against Mycobacterium smegmatis, with minimum inhibitory concentrations of 62.5-500 mu g/mL, indicating their potential use as antituberculous agents.Karadeniz Technical University Research Fund, Turkey [KTU-BAP-02 FHD5395]This study was supported by grants from Karadeniz Technical University Research Fund (KTU-BAP-02 FHD5395), Turkey

Novel 2-amino-4-aryl-6-pyridopyrimidines and N-alkyl derivatives: Synthesis, characterization and investigation of anticancer, antibacterial activities and DNA/BSA binding affinities

aydin, ali/0000-0002-9550-9111WOS: 000535446600002PubMed: 32272366A series of new 2-amino-4-aryl-6-pyridopyrimidines, and their N-alkyl bromide derivatives were designed and synthesized by employing methyl substituted azachalcones. These novel compounds were evaluated and compared to the well-known chemotherapeutics in terms of their anti-cancer and anti-microbial functions, and their DNA/protein binding affinities. in order for the cell proliferation, cytotoxicity and microdilution features to be observed, various cancer cell lines (Hep3B, A549, HeLa, C6, HT29, MCF7) were treated with 2-amino-4-aryl-6-pyridopyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c, 5a-c, 6a-c, 8a-c, 9a-c). Studies on the cells revealed that both pyrimidines and their alkyl derivatives (i) have a high anti-proliferative and antimicrobial activities, (ii) cause cell rounding, cytoplasmic blebs, and anomalous globular structure, and (iii) strongly bound to DNA/BSA macromolecules. Especially the length of the alkyl chain of the N-alkyl bromides has an increasing effect on the antiproliferative, antibacterial and cytotoxic functions, also DNA/protein binding affinity. Those results indicate the novel compounds to be promising antiproliferative agents, and their anticancer potential makes them candidates to be used for cancer therapy.Karadeniz Technical UniversityKaradeniz Technical University; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK-114R025]This study was supported by grants from Karadeniz Technical University and the Scientific and Technological Research Council of Turkey (TUBITAK-114R025)

Synthesis and biological evaluation of new 2,4,6-trisubstituted pyrimidines and their N-alkyl derivatives

Peker, Kivanc Derya Derya/0000-0002-8887-3505; aydin, ali/0000-0002-9550-9111WOS: 000458609100059PubMed: 30471580A series of new 2,4,6-trisubstituted pyrimidines and their N-alkyl bromide derivatives were prepared based upon methoxy substituted azachalcones as the starting materials. All newly synthesized compounds were screened for their anti-proliferative, cytotoxic, antibacterial activities and DNA/protein binding affinity. in vitro cell proliferation inhibitory and cell cytotoxic effects of 2,4,6-trisubstituted pyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c, 5a-c, 6a-c, 8a-c, 9a-c) were obtained with the help of the 3[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cell proliferation, LDH cytotoxicity detection, and microdilution assays. the antimicrobial activity for these compounds was also evaluated following the European Pharmacopoeia 8.0 protocol. the interactions of these compounds with DNA or bovine serum albumin were investigated by the spectrophotometric titration method. When the cytotoxic analysis and anticancer properties of the compounds were examined, most of the compounds significantly exhibited an anti-proliferative potency on cancer cells (IC50 similar to 2-10 mu g/mL) and caused a cytotoxic effect as low as control drugs, 5-fluorouracil, and cisplatin (similar to 7-15%). Because the compound-DNA adducts are hyperchromic or hypochromic, they caused variations in their spectra. This situation shows they can be linked to DNA by the groove binding mode at a binding constant range of 2.0 x 104 and 2.4 x 105 M-1. the antimicrobial screening results revealed that our new compounds for some human Gram( + ) and Gram( - ) pathogen bacteria showed remarkable activity with MIC values between < 7.81 and 125 mu g/mL. Overall, incorporation of alkyl chain to pyrimidines in the generation of N-alkyl bromides has resulted in showing differences in DNA/protein binding affinity, along with anti-proliferative and cytotoxic activity in favor of new compounds.Karadeniz Technical UniversityKaradeniz Technical University; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK-114R025]This study was supported by grants from Karadeniz Technical University and the Scientific and Technological Research Council of Turkey (TUBITAK-114R025)

Design, syntheses, theoretical calculations, MM-GBSA, potential anti-cancer and enzyme activities of novel Schiff base compounds

In this study, new Schiff base compounds (SB-F-OH, SB-Cl-OH and SB-Br-OH) were derived from chalcone-derived amine compounds containing halogen groups and 4-hydroxybenzaldehyde. Also, their phthalonitrile compounds (SB-F-CN, SB-Cl-CN and SB-Br-CN) have been synthesized. The structures of these compounds were elucidated by NMR, FT-IR and Mass spectroscopic methods. The quantum chemical parameters were calculated at B3LYP/6-31++g(d,p), HF/6-31++g(d,p) and M062X/6-31++g(d,p) levels. As the biological application of the synthesized compounds, (i) their inhibition properties of the synthesized compounds on Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) metabolic enzymes were investigated, and their potential anticancer activities against neuroblastoma (NB; SH-SY5Y) and healthy fibroblast (NIH-3T3) cell lines were determined by in vitro assays. All compounds showed inhibition at nanomolar level with the Ki values in the range of 97.86 +/- 30.51-516.82 +/- 31.42 nM for AChE, 33.21 +/- 4.45-78.50 +/- 8.91 nM for BChE, respectively. It has been determined that all tested compounds have a remarkable cytotoxic effect against SH-SY5Y, and IC50 values were significantly lower than NIH-3T3 cells. The lowest IC50 value was observed in SB-Cl-OH (7.48 +/- 0.86 mu M) and SB-Cl-CN (7.31 +/- 0.69 mu M). The molecular docking of the molecules was also investigated using crystal structure of AChE enzyme protein (PDB ID: 4M0E), crystal structure of BChE protein (PDB ID: 6R6V) and SH-SY5Y cancer protein (PDB ID: 2F3F, 3PBL and 5WIV). The ADME properties of the compounds were investigated. MM/GBSA method is calculated binding free energy. Afterwards, ADME/T analysis was performed to examine the some properties of the molecules.Communicated by Ramaswamy H. Sarm