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In this study, we performed the pharmacophore modeling and 4D-QSAR research of alkynylphenoxyacetic acid analogues as CRTh2 receptor opponent agents by utilizing the electron conformational genetic algorithm method. Quantum chemical calculations and conformational analyses of the compounds were carried out at HF/6-31G* level. Then electron conformational matrices of congruity were prepared for each conformer of each compound, which are represented by electronic and structural properties. As a result of the comparison of the matrices that are called electron conformational submatrices of activity, the pharmacophoric group of the compounds responsible for the activity was found at the determined tolerance intervals. The genetic algorithm and nonlinear least squares regression methods were applied to estimate the conjectural activity and investigate the most reliable molecular identifiers as feature selection from a large parameter pool. The compounds in the dataset were randomly segregated for training (61 compounds) and test sets (25 compounds) for statistical analysis. Validation of the 4D-QSAR model was appraised by the leave-one-out cross-validation technique. For the best model the r 2 training , r 2 test , q 2 , q 2 ext1 , q 2 ext2 , and q 2 ext3 values were found to be 0.

Background: An extensive study of 19 pyrazole derivatives were carried out based on the evaluation of DNA cleavage properties, antimicrobial and cytotoxic activities and 4D-QSAR analysis including pharmacophore modelling and bioactivity prediction by the Electron Conformational-Genetic Algorithm (EC-GA) method. Methods: The pyrazole derivatives were tested for their antimicrobial activity against certain human pathogenic organisms using the agar diffusion procedure. Binding of compounds with DNA was studied by gel electrophoresis using plasmid pBR322 DNA. The compounds were investigated for their properties as cytotoxic agents by brine shrimp lethality bioassay. To identify the pharmacophoric elements and find out the most important molecular properties which govern cytotoxic activity, multiple conformations of the compounds were used. Results: The urea derivatives of pyrazole had higher antibacterial activities against Gram-negative bacteria than against Gram-positive bacteria. Many of the compounds were found to cleave plasmid pBR322 DNA from the supercoiled form to the nicked circular. The cytotoxicity values of the compounds ranged from 13.87 to 84.1 µg/mL. The generated QSAR model was evaluated through the use of the Leave-One-Out Cross Validation (LOO-CV) method. A statistically significant and considerably predictive QSAR model was obtained with 4- descriptors resulting in R2 training =0.8223, R2 test =0.9346, q2=0.6201, q2 ext1=0.8672, q2 ext2= 0.8662 and q2 ext3=0.9511. Discussion: The generated model demonstrates that geometrical parameters are more correlated with cytotoxic activity. The resulting EC-GA model would provide benefits to design novel bioactive pyrazole derivatives which are more potent and have less side effects. Conclusion: It is believed that the generated QSAR model gives insight into developing new more potent pyrazole derivative drugs.

Çalışmanın amacı: Likenler, çeşitli elementler açısından hem doğal hem de yapay kaynaklı çevresel kirliliğin biyolojik göstergeleridir. Türkiye’nin farklı bölgelerinden toplanmış Cladonia cinsine ait 9 örnekte (Cladonia coniocraea, C. fimbriata, C. firma, C. foliacea, C. furcate, C. pocillum, C. pyxidata, C. rangiformis and C. subulata) Alüminyum, Krom, Mangan, Demir, Kobalt, Nikel, Bakır, Çinko, Arsenik, Selenyum, Stronsiyum, Kadmiyum, Kalay, Cıva ve Kurşun element miktarları araştırılmıştır. Çalışma alanı: Türkiye’de 7 farklı ilde yapılmış arazi çalışmalarında aynı cinse ait liken örnekleri toplanmıştır. Materyal ve yöntem: Tüm örnekler bağımsız olarak mikrodalga sistemde asit ortamında çözünürleştirildikten sonra ve üç paralel halinde analiz edilmiştir. Sonuçların doğruluğu, 1.547 Şeftali Yaprağı sertifikalı referans materyalin analiziyle onaylanmıştır. Temel sonuçlar: Metallerin kaynakları, metal birikim mekanizmaları ve likenler tarafından ne kadar absorblandıkları belirlenmiştir. Cladonia firma’da en yüksek Al, Cr, Ni konsantrasyonları sırasıyla 429.3, 3.04, 13.53 µg/g'dır. Cladonia subulata'da en yüksek Co, Sr, Cu, Se, Hg konsantrasyonları sırasıyla 0.81, 33.59, 13.16, 0.158, 0.060 µg/g'dır. Cladonia pyxidata'da en yüksek Pb, Cd, Sn konsantrasyonları sırasıyla 5.90, 0.30, 6.50 µg/g'dır. En yüksek Fe, Mn, Zn, As konsantrasyonları sırasıyla 228.7, 17.8, 26.44, 1.335 µg/g'dır. Araştırma vurguları: Sonuçlar likenlerde metal birikiminin doğrudan likenlerin toplandığı ortamla ilişkili olduğunu göstermiştir.