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 µM) and SB-Cl-CN (7.31 ± 0.69 µM). 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. Sarma.

Analysis of Volatile Constituent by Hydrodistillation and Solid-Phase Microextraction Techniques and Antimicrobial and Scolicidal Activities of Essential Oil and Soxhlet Extracts of Ulva rigida grown in Turkey.

In the present study, the volatile composition of Ulva rigida (U. rigida) was elucidated by two different methods. As a result of the identification process of volatile components using the GC/MS-FID instrument, 31 compounds were identified by hydrodistillation (HD) method, and 15 compounds were identified by solid-phase microextraction (SPME) method, elucidating the structure of 99.86 % and 92.65 %, respectively. The most abundant compounds in the essential oil of U. rigida were n-hexadecanoic acid and pentadecanal, while the most abundant compound according to the SPME analysis was heptadecyne, a hydrocarbon compound. In the next step, hexane, dichloromethane, chloroform and methanol solvent extracts of U. rigida were prepared and the antimicrobial activities of the extracts and the essential oil obtained by hydro-distillation as well as the scolicidal activities of the solvent extracts were determined. The results of the antimicrobial activity test of the essential oil showed a high level of activity against Bacillus cereus ATCC 10876 and MRSA. The highest activity was found on the microorganism of Pseudomonas aeruginosa ATCC 9027 in chloroform and methanol extracts of U. rigida. Furthermore, viability detection was performed and the scolicidal effects of the extracts on protoscoleces were assessed. The values of lethal concentration doses (LD50 , LD75 and LD90 ) were calculated using probit analysis.

Synthesis of some new isoxazole compounds and their biological tyrosinase and antioxidant activities.

In this study, 7 new isoxazole compounds (8-14) were synthesized from the cyclization of chalcone compounds (1-7) containing different functional groups with hydroxylamine hydrochloride in alkaline medium. Tyrosinase and antioxidant properties of 8-14 were investigated. IC50 values for the tyrosinase enzyme inhibition of compounds 8, 11, 12, and 13 were varied between 61.47 ± 3.46 and 188.52 ± 5.85, while compounds 9, 10 and 14 did not show any inhibition effect. The antioxidant properties of 8-14 were investigated by DPPH and CUPRAC methods. Compound 12 showed the best DPPH radical scavenging activity (SC50: 40.21 ± 2.71), while 12 and 13 had shown the greatest Cupric ion reducing effect as 1.233 ± 0.015 and 1.245 ± 0.019 mg TEAC/mg, respectively. As a result, the change of functional groups in the synthesized compounds caused a significant difference in the biological properties of 8-14.

Chemical Variation, Antimicrobial, Nitric Oxide Scavenging Activities and Tyrosinase Inhibition of Essential Oils and Solvent Extracts from Filipendula vulgaris Moench Growing in Turkey.

Volatile organic compositions of the essential oils (EOs), solid-phase microextraction (SPME) and SPME of n-hexane extracts from the flower and stem-leaf of Filipendula vulgaris (F. vulgaris) were analyzed by GC-FID/MS. A total of 107 constituents were characterized, flower and stem-leaf parts of the plant were found to contain different volatile organic compounds. Tricosane (29.6%), n-nonanal (20.5%) were identified as the main components in the essential oil of the flower, while phytol (35.2%) was found to be a major constituent in the essential oil of stem-leaf. Benzaldehyde (56.0%) and n-nonanal (31.6%) were the major groups in the SPME of stem-leaf and flower, respectively. The volatiles for the SPME of n-hexane extracts of the flower and stem-leaf of F. vulgaris were predominated by aromatic compounds (75.0% and 78.5%) and ketones (18.1% and 10.1%), respectively. On the other hand, a total of terpene compounds was found at the most in the EO of the stem-leaf part of the plant (48.6%). In addition, antimicrobial, tyrosinase inhibition, and nitric oxide scavenging activities of the n-hexane (H), methanol (M), aqueous extracts (A) and EOs of F. vulgaris were investigated. EOs and methanol extracts of flower and stem-leaf had high antimicrobial activity against tested various microorganisms. However, n-hexane extracts of the flower and stem-leaf only displayed activity against Mycobacterium smegmatis. Methanol extracts of flower and stem-leaf possessed the best tyrosine inhibition and NO scavenging activity.

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

A 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 anti-microbial 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 anti-cancer potential makes them candidates to be used for cancer therapy.

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

A 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 ∼ 2-10 µg/mL) and caused a cytotoxic effect as low as control drugs, 5-fluorouracil, and cisplatin (∼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 × 104 and 2.4 × 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 µg/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.