Browsing by Author "Okullu, Sinem Oktem"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Design, Synthesis, and Molecular Docking Studies of a Conjugated-Thiadiazole Thiourea Scaffold as Antituberculosis Agents
    (PHARMACEUTICAL SOC JAPAN, 2016-01-01) Tatar, Esra; Karakus, Sevgi; Kucukguzel, Sukriye Guniz; Okullu, Sinem Oktem; Unubol, Nihan; Kocagoz, Tanil; De Clercq, Erik; Andrei, Graciela; Snoeck, Robert; Pannecouque, Christophe; Kalayci, Sadik; Sahin, Fikrettin; Sriram, Dharmarajan; Yogeeswari, Perumal; Kucukguzel, Ilkay
    In view of the emergence and frequency of multidrug-resistant and extensively drug-resistant tuberculosis and consequences of acquired resistance to clinically used drugs, we undertook the design and synthesis of novel prototypes that possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole in a single molecular backbone. Three compounds from our series were distinguished from the others by their promising activity profiles against Mycobacterium tuberculosis strain H(37)Rv. Compounds 11 and 19 were the most active representatives with minimum inhibitory concentration (MIC) values of 10.96 and 11.48 mu m, respectively. Compound 15 was shown to inhibit M. tuberculosis strain H(37)Rv with an MIC value of 17.81 mu m. Cytotoxicity results in the Vero cell line showed that these three derivatives had selectivity indices between 1.8 and 8.7. In order to rationalize the biological results of our compounds, molecular docking studies with the enoyl acyl carrier protein reductase (InhA) of M. tuberculosis were performed and compounds 11, 15, and 19 were found to have good docking scores in the range of -7.12 to -7.83 kcal/mol.
  • No Thumbnail Available
    Item
    In Vitro Efficacy of the Venome of Black Scorpion (Androctonus crassicauda) on Leishmania tropica Promastigotes
    (ANKARA MICROBIOLOGY SOC, 2021-01-01) Zeyrek, Fadile Yildiz; Toprak, Sahin; Okullu, Sinem Oktem; Gurses, Gulcan; Doni, Nebiye Yentur; Kurt, Ozgur
    Scorpion venom is a substance that shows strong neurotoxic effects with its complex protein content and thus plays an important role for the scorpion in catching and digesting the hunt. Human body stung by a scorpion can show life-threatening systemic effects in a short time, ranging from erythema, pain, edema and local fever to abdominal pain, nausea and vomiting, diplopia and even coma. Scorpion venome is known to possess antimicrobial activity, and some of its compounds have potent antibacterial and antifungal activities. Leishmaniasis is a common vector-borne parasitic infection caused by Leishmania sp. protozoa and can lead skin, mucosa and fatal internal organs involvement in patients. There is a need for new drugs in the treatment of leishmaniasis, because it has been documented lately that there is a growing resistance against antimonial compounds which have been used in its treatment for decades. Leishmania species are known to be susceptible to antimicrobial peptides that act as ion-channel inhibitors, which are known to be present in scorpion venome. In this study, it was aimed to investigate the anti-leishmanial activity of scorpion venome extract obtained from Androctonus crassicauda species in our country. In this context, Leishmania tropica promastigotes which were thawed from liquid nitrogen in our laboratory and first grown in NNN and then RPMI-1640 media, were exposed to different dilutions of the extract containing A.crassicauda venom and meglumine antimonate used in the standard treatment of leishmaniasis and the efficacies on the promastigotes were compared and measured in vitro. This was followed by XTT cell viability test, which assessed whether anti-leishmanial dose of the extract was lethal for human cells or not. Trials showed that the half maximal inhibitory concentration (IC50) values of the venome extract and meglumine antimoniate were 18.12 mu g/ml (17.33-18.94) and 8.411 mu g/ml (7.922-8.927), respectively. This preliminary study showed that scorpion venome can be lethal on L.tropica promastigotes in vitro, on relatively higher doses compared to meglumine antimonate. Next step will be to determine the anti-leishmanial proteins in the extract and thus to identify new drug candidates with more specific studies.