Ahmet Kayraldiz

Human carbonic anhydrase (hCA) isoenzymes participate in essential pH-regulatory processes, but conservation of their catalytic sites makes selective inhibition difficult. We developed a direct pairwise machine learning framework for selectivity among hCA I, II, IX, and XII using curated Ki data from ChEMBL. Compounds entered a binary task only when one isoenzyme was strongly inhibited (Ki ≤ 200 nM) and the paired isoenzyme was weakly inhibited (Ki > 800 nM). A provenance-conservative STRICT analysis and a BROAD sensitivity analysis were evaluated under train-only split selection, hyperparameter optimization, and a globally locked outer-test protocol. The highest observed held-out performance was obtained for CA II/CA XII (MCC = 0.748) and CA IX/CA XII (MCC = 0.718), whereas CA II/CA IX was intermediate (MCC = 0.459) and CA-I-containing tasks were generally more difficult. Because the highest point estimates arose from relatively small test cohorts, these findings should be regarded as promising and require independent external or prospective validation. All six STRICT models exceeded 100 randomized-label controls (empirical p = 1/101 ≈ 0.0099, the resolution floor for 100 permutations). Applicability domain and SHAP analyses indicated pair-specific signals compatible with known isoenzyme-dependent active-site differences. Overall, the framework prioritizes interpretable hCA selectivity hypotheses while explicitly defining current uncertainty and validation limits.

In recent years, studies that investigate the effects of chemical compounds on organisms have increased in direct proportion to their widespread use. In this study, four different bidentate imine ligands and bidentate imine ligands+Cu(II) complexes were synthesized from the bioactive synthetic diarylmethylamine compound. After the ligands and metal complexes obtained were purified using chromatographic and analytical methods, their mutagenic effects were investigated with the Ames/Salmonella test system. In addition, interactions of four different Cu(II) complexes with B-DNA were evaluated with molecular docking analysis. Accordingly, the results indicated a significant increase in the colonies formed in the presence (+S9) and absence (-S9) of the metabolic activation system, meaning a mutagenic effect against strain TA98 and TA100 strains in general.

Vigabatrin (VGB) is a gammaaminobutyric acid-ergic (GABA-ergic) antiepileptic drug (AED) and is one of 2 approved drugs available to treat infantile spasms (IS). The aim of this study is to elucidate conflicting data on the toxic effects of VGB and to obtain detailed information about its possible cytogenotoxic effects in human lymphocytes. For this purpose, in vitro Chromosomal Aberration (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests, and Comet Assay were performed to determine possible genotoxic and cytotoxic effects of VGB. In addition, the binding energy level of VGB to DNA was determined in silico by molecular docking. The highest concentration (80 μg/ml) of VGB increased the SCE, CA, MN and micronucleated binuclear cell (BNMN) frequency significantly compared to the control after 24 and 48 hours of treatment. In the tail density and tail length parameters, the dose-dependent increase was found to be statistically significant compared to the control. At the 40 and 80 μg/ml concentrations of VGB for 48 hours caused a statistically significant increase in both CA/Cell and AC percentages, while MI and NDI decreased only significantly at the highest concentration (80 µg/ml) causing. In the Comet Assay head density, tail density and tail length parameters, the dose-dependent increase was found to be statistically significant compared to the control. Also, the in silico molecular docking analysis showed that VGB interacts with B-DNA close to the threshold binding energy. The lowest negative free binding energy (ΔG binding) was found as −5.13 kcal/mol. In conclusion, all results are evaluated together, it has been determined that VGB has cytogenotoxic effects in vitro and binds to DNA in silico with significant free binding energy.

Two different drug groups, typical (classic) and atypical (new), are used in the treatment of schizophrenia. Aripiprazole, an atypical antipsychotic chemical, is the active ingredient of the drug Abilify. This study was conducted to determine the possible genotoxic effect of aripiprazole. For this purpose, four different doses of aripiprazole (5; 10; 20, and 40 µg/mL) were examined with Chromosome Abnormality (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests. Based on these tests, Proliferation Index (PI), Percent Abnormal Cells (AC), Mitotic Index (MI), Micronuclear Binuclear Cell (MNBN), and Nuclear Division Index (NDI) levels were determined in human peripheral lymphocytes treated for 24 and 48 hours. Also, to determine possible binding sites of Aripiprazole on B-DNA molecular docking analysis was performed using AutoDock 4.0 (B-DNA dodecamer, PDB code: 1BNA). Aripiprazole binds to B-DNA with a very significant free binding energy (–11.88 Kcal/mol). According to our study, aripiprazole did not significantly change SCE, CA, AC percentage, MN frequencies when compared with control. According to these results, aripiprazole does not have a genotoxic effect. At the same time, no significant change was observed in the PI, MI, and NDI frequencies when compared with the control. In line with these results, it was observed that the use of aripiprazole in the treatment of schizophrenia did not pose any acute genotoxic and cytotoxic risk.

Cucurbitaceae familyası, dünya çapında ekonomik değer ve besin değeri açısından önemli birçok türü içerir. Son yıllarda yapılan moleküler genetik araştırmalara rağmen tarımsal öneme sahip kabak Cucurbita pepo L. türü ile ilgili genom bilgisi oldukça sınırlıdır. Bu çalışmanın esas amacı, genom spesifik markör sayısı son derece az olan kabak genomuna özgün yeni ve çok sayıda SSR markörlerinin (Basit Dizi Tekrarları) geliştirilmesidir. Kabak referans genomu tekrar motifleri açısından biyoinformatik araçlar ile taranmış ve kabak genomuna spesifik toplam 76744 adet aday SSR lokusu bulunmuştur. Çalışma kapsamında ilk kez çerezlik kabak kromozomlarını kapsayacak şekilde toplam 52303 adet SSR markörü geliştirilmiş ve üretilen markörlere ait bilgiler veri tabanlarına yüklenmiştir. Bu çalışmada, en fazla rastlanan SSR motiflerinin çoğunluğu AT/AT bakımından zengin olan di-nükleotit tekrarları olarak tespit edilmiştir. Geliştirilen yeni SSR markörlerin amplifikasyon durumu ve polimorfik bant üretme gücünü test etmek amacı ile 39 adet çerezlik kabak (Cucurbita pepo L.) genotipinden oluşan bir koleksiyon karakterize edilmiş ve SSR alelleri, var/yok (1/0) şeklinde skorlanmış olup veri dosyası DARwin6 programında genetik çeşitlilik analizlerine tabi tutulmuştur. Çalışma sonuçları ile, kabak genomiğine önemli moleküler genetik markörler kazandırılarak ilerde yapılacak moleküler ıslah ve haritalama çalışmaları için önemli bilgiler kazandırılabileceği düşünülmektedir.

Öz Amaç: HIV (Human Immünodeficiency Virus) enfeksiyonunun tedavisinde kullanılan antiretroviral ilaçlar, HIV virüsünün vücutta çoğalmasını ve etkinleşmesini engelleyerek tedavi sağlarlar. Bu ilaçlar virüsü eradike etmediğinden, hastaların viral replikasyonu baskılamak amacıyla ilaçları ömür boyu kullanmaları gerekmektedir. Bu çalışmada antiretroviral ilaçlardan birisi olan tenofovir disoproksil fumaratın insan periferal lenfositlerindeki in vitro genotoksik aktivitesi araştırılmıştır. Gereç ve Yöntem: Bu maçla hücreler, tenofovir disoproksil fumaratın dört farklı konsantrasyonuyla (2,5, 5, 10, 20 µg/ml) 24 ve 48 saat süreyle muamele edilmiştir. Tenofovir disoproksil fumaratın olası genotoksik aktivitesi için hücrelerdeki kardeş kromatid değişimi, kromozom anormalliği ve mikronükleus düzeyleri incelenmiştir. Sitotoksik etkiyi saptamak amacıyla muamele edilmiş hücrelerde ayrıca mitotik indeks, proliferasyon indeksi ve nükleer bölünme indeksi belirlenmiştir. Bulgular: Tenofovir disoproksil fumarat etken maddesinden hazırlanan dört farklı doz ile 24 ve 48 saat muamele edilen hücrelerde kardeş kromatid değişimi, kromozomal anormallik ve mikronükleus değerlerinde kontrol grubuna kıyasla önemli bir farklılık saptanmamıştır. Aynı şekilde tenofovir disoproksil fumarat etken maddesi ile muamelenin mitotik indeks, proliferasyon indeksi ve nükleer bölünme indeksi değerlerini etkilemediği gözlenmiştir. Sonuç: Bu çalışmada tenofovir disoproksil fumaratın insan periferal lenfositlerinde genotoksik ve sitotoksik etki göstermediği saptanmıştır.

Dirithromycin antibiotic is a 14-membered lactone ring macrolide and is widely used in medicine to treat many different types of bacterial infections. In the present study, the possible genotoxicity of dirithromycin was evaluated in cultured human lymphocytes by using sister chromatid exchanges (SCEs), chromosome aberration (CA), and micronucleus (MN) tests and also cell proliferation kinetics such as mitotic index (MI), replication index (RI), and nuclear division index (NDI) were analyzed for cytotoxicity. Cell cultures were treated with four different concentrations of dirithromycin (37.75, 67.50, 125, and 250 µg/mL) for 24 and 48 h periods. Dirithromycin significantly induced SCE and MN frequency at all concentrations in both 24 and 48 h treated cells. In addition, CA level has been markedly increased in the cells treated with almost all concentrations of dirithromycin for 24 (except 37.75 µg/mL) and 48 h treatment periods as compared to control. However, MI, RI, and NDI values were not affected by the dirithromycin treatment (p> 0.05). The results of this study indicated that dirithromycin treatment caused genetic damage by increasing the level of cytogenetic endpoints, suggesting its genotoxic and mutagenic action on human lymphocytesin vitro.