Abdurrahman Olğaç

Gazi University · Department of Pharmaceutical Chemistry

Drug discovery and development requires the integration of multiple scientific and technological disciplines in chemistry, biology and extensive use of information technology. Computer Aided Drug Discovery (CADD) methods are being used in this work area with several different workflows. Virtual screening (VS) is one of the most often applied CADD m...

AFMC‐AIMECS meetings are internationally organized biannually by the Asian Federation for Medicinal Chemistry (AFMC) and are focused on recent studies in drug discovery and development both in academia and industry. Member organizations of the AFMC are the Pharmaceutical Society of Japan, the Chinese Pharmaceutical Association, the Royal Australian...

Leukotrienes (LTs) are proinflammatory mediators derived from arachidonic acid (AA), which play significant roles in inflammatory diseases. 5-lipoxygenase-activating protein (FLAP) is an integral membrane protein, which is essential for the initial step in LT biosynthesis. The aim of this study was to discover novel and chemically diverse FLAP inhi...

5-Lipoxygenase-activating protein (FLAP) is a regulator of cellular leukotriene biosynthesis, which governs the transfer of arachidonic acid (AA) to 5-lipoxygenase for efficient metabolism. Here, the synthesis and FLAP-antagonistic potential of fast synthetically accessible 1,2,4-triazole derivatives based on a previously discovered virtual screeni...

In recent years, integration of in silico approaches to natural product (NP) research reawakened the declined interest in NP-based drug discovery efforts. In particular, advancements in cheminformatics enabled comparison of NP databases with contemporary small-molecule libraries in terms of molecular properties and chemical space localizations. Vir...

The inhibition of human microsomal prostaglandin E 2 (PGE 2) synthase-1 (mPGES-1) is a promising therapeutic modality for developing next-generation anti-inflammatory medications. In this study, we present novel 2-phenylbenzothiazole derivatives featuring heteroaryl sulfonamide end-capping substructures as inhibitors of human mPGES-1, with IC 50 va...

Microsomal prostaglandin E2 synthase 1 (mPGES-1) is a promising target for treating inflammatory diseases and pain. This study introduces a novel series of benzimidazoles, with the most potent analogs exhibiting IC50 values of 0.27–7.0 nM in a cell-free assay for prostaglandin (PG)E2 production. Compound 44 (AGU654) demonstrated remarkable selectiv...

We addressed the heteromerization of the epidermal growth factor receptor (EGFR) with G-protein coupled receptors (GPCR) on the basis of angiotensin-II-receptor-subtype-1(AT1R)-EGFR interaction as proof-of-concept and show its functional relevance during synergistic nuclear information transfer, beyond ligand-dependent EGFR transactivation. Followi...

Interleukin-2 (IL-2) is an important cytokine for treating metastatic renal cell carcinoma and melanoma. Aldesleukin is a therapeutic version of IL-2 produced by recombinant DNA technology. IL-2 interacts with IL-2Rα, IL-2Rβ and ƴc receptors. When it binds to the β, γ receptors it is aimed to fight cancer or binds α, β, γ receptors for treating aut...

Structurally diverse indole-3-pyrazole-5-carboxamide analogues (10-29) were designed, synthesized, and evaluated for their antiproliferative activity against three cancer cell lines (Huh7, MCF-7, and HCT116) using the sulforhodamine B assay. Some of the derivatives showed anticancer activities equal to or better than sorafenib against cancer cell l...

Discovering novel drug candidate molecules is one of the most fundamental and critical steps in drug development. Generative deep learning models, which create synthetic data given a probability distribution, have been developed with the purpose of picking completely new samples from a partially known space. Generative models offer high potential f...

Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), which are endowed with beneficial biological activities as they reduce inflammation, regulate endothelial tone, improve mitochondrial function, and decrease oxidative stress. Therefore, inhibition of sEH for maintaining high EET levels is implicated as a new therapeutic m...

Soluble epoxide hydrolase (sEH) is implicated as a potential therapeutic target for inflammation‐related pathologies in the context of cardiovascular, central nervous system and metabolic diseases. In our search for novel sEH inhibitors, we designed and synthesized novel analogs of the piperazine urea derivative 4, a previously discovered dual micr...

Microsomal prostaglandin E2 synthase-1 (mPGES-1) is recognized as a promising therapeutic target for next-generation anti-inflammatory drugs to treat inflammatory diseases. In this study, we report the identification of new, potent and selective inhibitors of human mPGES-1 such as compounds 10, 31 and 49 with IC50 of 0.03–0.09 μM in a cell-free ass...

Cardiovascular diseases are the primary reason for deaths in the world. However, antiplatelet drugs in the market have limitations in use because of the risk of increased bleeding and other side effects that impair primary homeostasis. Therefore, safe and effective antithrombotic drugs are needed for the treatment of plaque formation in blood vesse...

Novel compounds containing polar and nonpolar substitutions on the prop-2-en-1-on linker of the trans-indol-3-ylacrylamide scaffold were designed by modeling within the colchicine site of tubulin and then synthesized to determine the role of such substitutions on tubulin polymerization. We first determined the in vitro antiproliferation activities...

Interleukin-2 (IL-2) is an immunostimulatory cytokine and interacts with IL-2 receptors (IL-2Rs); IL-2Rα, IL-2Rβ, and ƴc receptor. IL-2 binds to β, γ receptors for fighting cancer or α, β, γ receptors for autoimmune diseases [1]. Aldesleukin was the therapeutic version of IL-2 and developed with minor modifications to the sequence of IL-2. There ar...

Microsomal prostaglandin E2 synthase-1 (mPGES-1), 5-lipoxygenase (5-LO) and 5- lipoxygenase-activating protein (FLAP) are key for biosynthesis of proinflammatory lipid mediators and pharmacologically relevant drug targets. In the present study, we made an attempt to explore the role of small heteroaromatic fragments on the 4,5-diarylisoxazol-3-carb...

ABSTRACT An individual's athletic ability is influenced by genetic and environmental factors. Some mitochondrial haplogroups and polymorphisms have been shown to be associated with human performance. The aim of this study is to asses whether the frequency distribution of mitochondrial haplogroups is an association between elite Turkish wrestlers a...

2,3-Benzodiazepine compounds are an important family of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists that act in a noncompetitive manner. Due to the critical role of AMPARs in the synapse and various neurological diseases, significant scientific interest in elucidating the molecular basis of the function of the...

Natural product-derived drugs can be extracts, biological macromolecules or purified small molecule substances. Small molecule drugs can be originally purified from natural products (NPs), can represent semi-synthetic molecules, natural fragment containing small molecules or are fully synthetic molecules that mimic natural compounds. New semi-synth...

Leukotrienes (LTs) and prostaglandin (PG)E2are enzymatically produced from arachidonic acid and represent highly bioactive lipid mediators with pro-inflammatory functions. Here, we report on novel multi-target inhibitors that potently and dually interfere with 5-lipoxygenase-activating protein (FLAP) and microsomal prostaglandin E2synthase (mPGES)-...

Pharmacological intervention with 5-lipoxygenase (5-LO) pathway leading to suppression of leukotriene (LT) biosynthesis is a clinically validated strategy for treatment of respiratory and cardiovascular diseases such as asthma and atherosclerosis. Here we describe the synthesis of a series of C(5)-substituted analogues of the previously described 5...

In this article, we report novel leukotriene (LT) biosynthesis inhibitors that may target 5-lipoxygenase-activating protein (FLAP) based on the previously identified isoxazole derivative (8). The design and synthesis was directed towards a subset of 4,5-diaryl-isoxazole-3-carboxylic acid derivatives as LT biosynthesis inhibitors. Biological evaluat...

Introduction: Sequence analysis of human mitochondrial DNA has been demonstrated to be a valid and reliable tool for discriminating between unrelated individuals. Noncoding, displacement (D) loop contains two hypervariable regions, HV I and HV II. These regions are highly polymorphic. The HV regions have been used extensively in forensic investigat...