Synthesis, characterization and docking studies of new chalcone derivatives carrying propargyl side chain as a monoaminoxidase inhibitor

Monoamin oksidazlar (MAO), endojen ve ekzojen aminlerin oksidatif deaminasyonundan sorumlu enzim ailesidir. MAO-A ve MAO-B olarak isimlendirilen iki izoformdan oluşan MAO enzimi nörotransmiterlerin metabolizmasındaki rollerinden dolayı nöropsikiyatrik ve nörodejeneratif bozuklukların tedavisi için ilaçların geliştirilmesinde önemli hedeflerdir. Özellikle MAO-B inhibitörlerinin Parkinson hastalığı (PH) ve Alzheimer hastalığı (AH) gibi en sık görülen nörodejeneratif hastalıkların tedavisinde sıklıkla tercih edildiği bilinmektedir. Bu amaçla, bu çalışma kapsamında yeni propargilşalkon türevleri sentezlenmiş ve yapı tayinleri 1H-NMR, 13C-NMR ve yüksek çözünürlüklü kütle spektroskopisi (HRMS) metotları kullanılarak aydınlatılmıştır. İn vitro aktivite testleri sonucunda elde edilen veriler 2c kodlu bileşiğin MAO-B inhibitörü olarak umut vaat edici olduğunu ortaya koymuştur. Gerçekleştirilen moleküler modelleme çalışmaları ile bileşik 2c’nin hMAO-B enzim aktif bölgesindeki bağlanma ve etkileşim noktaları belirlenmiştir.Monoamine oxidases (MAO) are a family of enzymes responsible for the oxidative deamination of endogenous and exogenous amines. The MAO enzyme, which consists of two isoforms named MAO-A and MAO-B, are important targets in the development of drugs for the treatment of neuropsychiatric and neurodegenerative disorders due to their role in the metabolism of neurotransmitters. It is known that MAO-B inhibitors are frequently preferred in the treatment of the most common neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). For this purpose, within the scope of this study, new propargyl-chalcone derivatives were synthesized and the structure determinations were elucidated using 1H-NMR, 13C-NMR and high-resolution mass spectroscopy (HRMS) methods. The data obtained as a result of in vitro activity tests showed that the compound 2c is promising as a selective MAO-B inhibitor. With the molecular modelling studies carried out, the binding and interaction points of the compound 2c in the hMAO-B enzyme active site were determined

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 and Anticandidal Activity of New Imidazole-Chalcones

In the present work, 15 new 1-(4-(1H-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (3a–3o) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (3a–3o) were characterized by IR, 1H-NMR, 13C-NMR, and LCMSMS spectroscopic methods. The anticandidal activity of compounds (3a–3o) against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata (ATCC 90030) was elucidated according to the EUCAST definitive (EDef 7.1) method. Consistent with the activity studies, 3a–3d were found to be more potent derivatives with their MIC50 values (0.78 µg/mL–3.125 µg/mL) against Candida strains. Compound 3c indicated similar antifungal activity to ketoconazole against all Candida species and was evaluated as the most active derivative in the series. Effects of the most potent derivatives 3a–3d on ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of the ergosterol level in C. krusei. Moreover, these compounds were subjected to a cytotoxicity test for the preliminary toxicological profiles and were found as non-cytotoxic. Furthermore, docking studies for the most active derivative 3c were performed to evaluate its binding modes on lanosterol 14-α-demethylase. In addition to in vitro tests, docking studies also revealed that Compound 3c is a potential ergosterol biosynthesis inhibitor

1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri

Amaç: Antifungal etkili ilaçların düzensiz kullanımı ile artan direnç gelişimi ve immün yetmezliği olan hastalarınsayısındaki artış nedeniyle, son yıllarda fungal enfeksiyonların tedavisindeki başarısızlık giderek artmaktadır. Bu sorun,daha etkin yeni antifungal ilaçlara olan ihtiyacı doğurmaktadır. Günümüzde antiülseratif, antihelmintik, antiviral,antihistaminik, antiinflamatuar ve antioksidan etkileri nedeniyle pek çok tedavi alanında kullanılmakta olanbenzotiyazol türevi bileşikler dikkat çekmektedir. Benzotiyazol halkası, DNA bazlarının (pürin ve pirimidinçekirdekleri) temel yapılarının izosteri olduğundan ve triptofan gibi aminoasitlerin doğal olarak yapısındabulunduğundan canlı organizmalar tarafından tanınmaktadır. Pek çok araştırma, benzotiyazol halkasının antifungalaktivitesini de kanıtlamıştır.Gereç ve Yöntemler: Beş yeni bileşikten oluşan 2-Sübstitüe-N-(6-(1,2,4-triazol-1-il)benzo[d]tiyazol-2-il)-asetamit (5a5e) serisi sentezlenmiştir. Elde edilen bileşiklerin yapıları FT-IR (fourier dönüşümlü kızılötesi spektroskopisi), 1HNMR (proton nükleer manyetik rezonans), 13C-NMR (karbon nükleer manyetik rezonans) ve kütle spektroskopisiverileri kullanılarak aydınlatılmıştır. Bileşiklerin in vitro antifungal aktivitesi microbroth dilüsyon yöntemi kullanılarakdört farklı Candida türüne (Candida krusei, Candida albicans, Candida parapsilosis ve Candida globrata) karşıdeğerlendirilmiştir. Ketakonazol referans ilaç olarak kullanılmıştır.Bulgular: Sentezlenen bileşiklerin minimum inhibitör konsantrasyon değerleri incelendiğinde orta derecede antifungalaktivite gösterdikleri görülmektedir. Sentezlenen bileşikler içerisinde 5c kodlu bileşik C. glabrata ve C. albicans’a karşıreferans ilaçtan daha yüksek etki göstermiştir.Sonuç: Sentezlenen bileşiklerin antifungal potansiyelleri incelendiğinde umut verici sonuçlara ulaşıldığı görülmektedir.Bu nedenle, bu çalışmanın sonuçlarına göre, projede kullanılan sentez yöntemlerine bağlı olarak, sentezlenecek olanyeni bileşiklerin antifungal aktivitelerinin araştırılması önerilmektedir

Synthesis and Antimicrobial Activity Evaluation of New Benzimidazole—Thiazole Derivatives

Antibiotic resistance which was expedited by the use of antimicrobial drugs has been a significant global challenge for public health [1]. [...

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR), 13C Nuclear Magnetic Resonance Spectroscopy (13C-NMR) and Electronspray Ionisation Mass Spectroscopy (ESI-MS) spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST) and modified forced swimming (MFST) methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg) was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives

Synthesis and Anticandidal Activity of New Imidazole Derivatives

During the last few years, there has been an increased awareness of morbidity and mortality related to invasive and systemic fungal disease because of resistant fungi and immunocompromised infections, for instance, AIDS. [...

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. [...

Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC50 value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The Ki values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound