Browsing by Author "Uygun, Meltem Tan"

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Computer Assisted Interaction of Cathepsin L Enzyme and Pyrazolopyrazinone Compounds and Investigation of Anticancer Properties
(2022) Kına, Kamile; Uygun, Meltem Tan
Kanserle mücadelede birçok biyolojik faktörün etkinliği ve rolü araştırılmakla beraber yeni terapötik ajanların keşfi ve sentezi oldukça önemlidir. Son zamanlarda yapılan çalışmalar göstermiştir ki proteaz enzim ailesinin mensubu olan katepsin L enziminin kanser tedavisinde etkinliği büyük bir önem arz edip üzerinde yapılan çalışmalar giderek artmaktadır. Birçok kanser türü üzerinde etkinliği araştırılan katepsin L'nin farklı biyolojik ajanlarla inhibisyonunun buna sebep olduğu düşünülmektedir. Bu noktadan hareketle, bu çalışmada pirazolopirazinon bileşiklerinin (KK1-KK8) katepsin L enzimi ile in silico etkileşimi sonrasında inhibisyon özellikleri araştırılmıştır. Araştırma sonucunda mevcut 8 ligandın sentezi düşünülecek olursa, öteki moleküller ile kıyaslandığı zaman KK8 molekülü potansiyel katepsin L inhibitörü olduğundan, yapılacak sentez çalışmalarına bu liganddan başlanması önerilir. Elde edilen bulgular literatür çerçevesinde ele alınmıştır.
A New Synthetic Approach for Pyrazolo[1,5-A]pyrazine Derivatives and Their Antiproliferative Effects on Lung Adenocarcinoma Cell Line
(Springer, 2022) Uygun, Meltem Tan; Amudi, Karina; Turacli, Irem Dogan; Menges, Nurettin
Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160 mu M concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure-activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable.
Synthesis of Spiroindolenine-Cyclopentenedione Skeletons and Their Chemical Behaviours: the First Example of a Lactone-Type Spiroindolenine Structure
(Royal Soc Chemistry, 2022) Uygun, Meltem Tan; Menges, Nurettin
A manageable, one-pot, and high-yield protocol for synthesising highly reactive spiroindolenine derivatives is reported. Spiroindolenines are furnished by a reaction between DCC (dicyclohexylcarbodiimide) and indole-3-butenoic acid derivatives. The protocol proposed here involves the construction of a carbon-carbon bond through intramolecular domino cyclisation. The reaction mechanism for spirocyclisation is discussed; both NMR and X-ray analysis were used to verify the structure of spiroindolenine. The applied strategy allowed the formation of spiroindolenine with a dione substructure, which is an unknown compound with a spirocyclic nucleus. Further reactions of spiroindolenines with di-amines, a primary amine, and alcohol have been reported, and new types of indole derivatives, such as indoloquinoxalines, where the spirocentre atom undergoes a nucleophilic attack, are yielded.