Bazı benzotiyazol türevlerinin antifungal aktivitesinin değerlendirilmesi

The antifungal activity of the previously synthesized compounds was evaluated in order to provide solutions to the candida-induced diseases in animals. In the present study, 10 benzothiazole derivatives (4a-4j) were resynthesized to evaluate their antifungal activity. IR, 1HNMR, 13C-NMR and HRMS (Infrared Spectroscopy, 1H Nuclear Magnetic Resonance Spectroscopy, 13C Nuclear Magnetic Resonance Spectroscopy, High Resolution Mass Spectrometry) spectroscopic methods, determined the structure of the synthesized compounds. MIC50(Minimum Inhibitory Concentration) values of the re-synthesized compounds against Candida species were evaluated by in vitro experiments. As a result of activity studies, it was found that compounds 4c and 4d showed significant activity. Compound 4d was found to be the most potent derivative against Candida krusei with a MIC50 value of 1.95 µg / mL.Hayvanlarda oluşan candida kaynaklı hastalıklara çözüm üretmek amacıyla daha önceden sentezi yapılmış bileşikler benzer metot kullanarak tekrar sentezlenmiş ve antifungal etkinlikleri değerlendirilmiştir. Mevcut çalışmada, 10 tane benzotiyazol türevi bileşik (4a-4j), antifungal aktivitelerini değerlendirmek üzere yeniden sentezlenmiştir. Sentezlenen bileşiklerin yapı tanımlamaları IR, 1HNMR, 13C-NMR ve HRMS (Kızılötesi Spektroskopi, 1H Nükleer Manyetik Rezonans Spektroskopisi, 13C Nükleer Manyetik Rezonans Spektroskopisi, Yüksek Çözünürlüklü Kütle Spektrometresi) spektroskopik yöntemleri kullanılarak gerçekleştirilmiştir. Yeniden sentezlenmiş bileşiklerin Candida türlerine karşı MIC50 (Minimum İnhibitör Konsantrasyon) değerleri in vitro deneyler yapılarak değerlendirilmiştir. Yapılan aktivite çalışmaları sonucunda 4c ve 4d bileşikleri önemli aktivite göstermiştir. 4d bileşiğinin Candida krusei’ye karşı 1.95 µg / mL MIC50 değeri ile güçlü bir türev olduğu bulunmuştur

Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as possible anticancer agents

The synthesis of new N-(5-substituted-1,3,4-thiadiazol-2-yl)-2-[(5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio]acetamide derivatives and investigation of their anticancer activities were the aims of this work. All the new compounds’ structures were elucidated by elemental analyses, IR, 1H NMR, 13C NMR and MS spectral data. Anticancer activity studies of the compounds were evaluated against MCF-7 and A549 tumor cell lines. In addition, with the purpose of determining the selectivity of cytotoxic activities, the most active compound was screened against a healthy NIH3T3 cell line (mouse embryonic fibroblast cells). Among the tested compounds, compound 4y (N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-((5-(p-tolylamino)-1,3,4-thiadiazol-2-yl)thio)acetamide), showed promising cytotoxic activity against MCF7 cancer cell with an IC50 value of 0.084 ± 0.020 mmol L–1 and against A549 cancer cell with IC50 value of 0.034 ± 0.008 mmol L–1, compared with cisplatin. The aromatase inhibitory activity was evaluated for compound 4y on MCF-7 cell line showing promising activity with IC50 of 0.062 ± 0.004 mmol L–1

Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor

In the last step of estrogen biosynthesis, aromatase enzyme catalyzes the conversion of androgens to estrogens. Aromatase inhibition is an important way to control estrogen-related diseases and estrogen levels. In this study, sixteen of benzimidazole-triazolothiadiazine derivatives have been synthesized and studied as potent aromatase inhibitors. First, these compounds were tested for their anti-cancer properties against human breast cancer cell line (MCF-7). The most active compounds 5c, 5e, 5k, and 5m on MCF-7 cell line were subject to further in vitro aromatase enzyme inhibition assays to determine the possible mechanisms of action underlying their activity. Compound 5e showed slight less potent aromatase inhibitory activity than that of letrozole with IC50 = 0.032 ± 0.042 µM, compared to IC50 = 0.024 ± 0.001 µM for letrozole. Furthermore, compound 5e and reference drug letrozole were docked into human placental aromatase enzyme to predict their possible binding modes with the enzyme. Finally, ADME parameters (absorption, distribution, metabolism, and excretion) of synthesized compounds (5a–5p) were calculated by QikProp 4.8 software

Synthesis, molecular docking, in silico ADME and antimicrobial activity studies of some new benzimidazole-triazole derivatives

In this study, new benzimidazole-triazole derivatives were synthesized in two steps. First, 4-benzaldehyde derivatives are synthesized by reacting 1,2,4-triazole ring and 4-fluorobenzaldehyde. In the last step, the benzimidazole ring was obtained with o-phenylenediamine derivatives under microwave radiation. The structures of synthesized compounds were confirmed by 1 H-NMR, 13 C-NMR, infrared spectroscopy, mass spectroscopy, and elemental analysis. Antimicrobial activity of synthesized compounds is associated with six different types of bacteria (Escherichia coli ATCC 35218, E.coli ATCC 25922, Klebsiella pneumoniae NCTC 9633, Pseudomonas aeruginosa ATCC 27853, Salmonella typhimurium ATCC 13311, Staphylococcus aureus ATCC 25923), and four different Candida (C. albicans ATCC 24433, C. glabrata ATCC 90030, C. krusei ATCC 6258, C. parapsilosis ATCC 22019). Synthesized compounds showed weak antibacterial activity. However, 3a, 3b, and 3c compounds against C. albicans of the Candida species were found to show promising activity. Given the effect of substituents on antifungal activity, it is seen that the compounds 3a, 3b, and 3c carry chlorine, methyl, and fluoro substituents on the benzimidazole ring attract attention with higher activities. Molecular docking studies of 3a, 3b, and 3c were performed Schrödinger Glide XP against Candidas' sterol 14-alpha demethylase (CYP51), and estimated ADME calculations were analyzed.</p

Design, Synthesis Molecular Docking Study and Antifungal Activity Evaluation of New Benzimidazole-Triazole Derivatives

Lanosterol 14α-demethylase (CYP51) is an essential enzyme in the fungal life cycle and also an important target for antifungal drug development. Selective inhibition of the enzyme would cause depletion of ergosterol and accumulation of lanosterol and result in the growth inhibition of the fungal cell [1]. [...

BAZI YENİ KİNOKSALİN HİDRAZONLARIN SENTEZİ ve ANTİMİKROBİYAL AKTİVİTELERİ

10 yeni kinoksalin hidrazondan oluşan yeni bir grup aktimikrobiyal aktivitesi incelenmek üzere sentezlenmiştir. Bileşiklerin yapıları IR, 1H-NMR, MS spektral ve elemental analiz ile aydınlatılmıştır. Bileşiklerin antimikrobiyal aktiviteleri Mikro-broth dilüsyon yöntemi ile 3 fungus ve 7 bakteri türüne karşı değerlendirilmiştir. Sentezlenen bütün bileşikler Pseudomonas aeruginosa’ ya karşı önemli antibakteriyal aktivite göstermiştir. Ayrıca, 2,4-difloro yapısı içeren 4b bileşiği Pseudomonas aeruginosa’ ya karşı kloramfenikolden 2 kat daha iyi antibakteriyal aktivite göstermişti

Synthesis, Anticandidal Activity and Molecular Docking Study of Some New Imidazole Derivatives

The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents [1–3]. [...

Synthesis and Antimicrobial Activity of Newly Synthesized 2-((5-(4-(5(6)fluoro-1H-benzo[d]imidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio)-Derivatives

Benzimidazole derivatives have a great deal of interest in terms of antimicrobial therapy. [...

Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor

[Image: see text] In this study, a series of novel 1,3,4-oxadiazole-benzimidazole derivatives were designed and synthesized. Their cytotoxic activities against five cancer cell lines, including A549, MCF-7, C6, HepG2, and HeLa, were evaluated by the MTT assay. The compounds 5b,c showed satisfactory potencies with much higher anticancer activity in comparison to the reference drug doxorubicin against the studied cancer cell lines. In vitro, enzymatic inhibition assays of aromatase (ARO) enzymes were performed. Molecular docking, molecular dynamics simulations, and binding free energy analyses were used to better understand the structure–activity connections and mechanism of action of the aromatase inhibitors. Two types of satisfactory 3D-QSAR (CoMFA and CoMSIA) models were generated, to predict the inhibitory activities of the novel inhibitors. Molecular docking studies were also carried out to find their binding sites and types of their interactions with the aromatase enzyme. Additionally, molecular dynamics simulations were performed to explore the most likely binding modes of compounds 5b,c with CYP19A1

Design, synthesis, molecular modeling, DFT, ADME and biological evaluation studies of some new 1,3,4-oxadiazole linked benzimidazoles as anticancer agents and aromatase inhibitors

Breast cancer is the most frequent female cancer and second cause of cancer-related deaths among women around the world. Two thirds of breast cancer patients have hormone-dependent tumors, which is very likely be treated with hormonal therapy. Aromatase is involved in the biosynthesis of estrogen thus a critical target for breast cancer. In this study, in order to identify new aromatase enzyme inhibitors, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by H-1 NMR, C-13 NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5.165 +/- 0.211 mu M and 5.995 +/- 0.264 mu M against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking and dynamics simulations against aromatase enzyme was performed to determine possible protein-ligand interactions and stability. DFT study was performed to evaluate the quantum mechanical and electronic properties of compound 5a. Finally, the theoretical ADME properties of the potential aromatase inhibitor compound 5a were analyzed by calculations. Communicated by Ramaswamy H. Sarm