Papers by Sultan Nacak Baytas
Bioorganic & Medicinal Chemistry, 2014
European journal of medicinal chemistry, Mar 1, 2017
Despite having the second highest mortality associated with cancer, currently Sorafenib is the on... more Despite having the second highest mortality associated with cancer, currently Sorafenib is the only FDAapproved chemotherapeutic agent available for liver cancer patients which can only improve survival for few months. In this study, various pyrazolic chalcone analogous compounds were synthesized and evaluated as potential chemotherapeutic agents for the treatment of hepatocellular carcinoma (HCC). Modifying the central pyrazole ring at the C(3)-position with different heteroaryl rings and substituting the C(4)-position of pyrazole with differently substituted chalcone moiety produced fouthy two variant compounds. For all these compounds, cytotoxicity was evaluated using sulforhodamine B assay and real time cell growth tracking, respectively. Based on 50% inhibitory concentration (IC 50) values, compounds 39, 42, 49, and 52 were shown to exhibit potent cytotoxic activity against all the cancer cell lines tested, and had better cytotoxic activities than the well-known chemotherapeutic drug 5-FU. Therefore, these compounds were chosen to be further evaluated in a panel of HCC cell lines. Flow cytometric analysis of HCC cells treated with compounds 39, 42, 49, and 52 demonstrated that these compounds caused cell cycle arrest at G2/M phase followed by the apoptotic cell death and impaired cell growth as shown by real-time cell growth surveillance. Consistent with these results, western blotting of HCC cells treated with the compounds resulted in molecular changes for cell cycle proteins, where p21 levels were increased independent of p53 and the levels of the key initiators of mitosis Cyclin B1 and CDK1 were shown to decrease upon treatment. In conclusion, chalcone derivatives 42 and 52 show potent bioactivities by modulating the expression of cell-cycle related proteins and resulting in cell-cycle arrest in the HCC cell lines tested here, indicating that the compounds can be considered as preclinical candidates.
MedChemComm, 2018
With the aim of achieving new compounds possessing both anti-inflammatory and antiplatelet activi... more With the aim of achieving new compounds possessing both anti-inflammatory and antiplatelet activities, we synthesized (E)-3-[3-(pyridin-3/4-yl)-1-(phenyl/sulfonylmethylphenyl)-1H-pyrazol-4-yl]acrylamides, and evaluated their COX-1 and COX-2 inhibitory and antiplatelet activities. Since COX-2 inhibitory and antiplatelet compounds have anticancer potential, we also screened their antiproliferative effects against three human cancer cell lines. Compounds 5n, 5p, 5s, 10d, 10g and 10i were determined as dual COX-2 inhibitor/antiplatelet compounds. Compound 10h appeared to be a compound that exhibited antiplatelet activity without inhibiting the COX enzyme. Compounds 5h, 10a and 10i were the most effective derivatives which displayed antiproliferative activity against Huh7, MCF7 and HCT116 cells. Particularly, compound 10i, as the compound exhibiting the highest cytotoxic, antiplatelet and COX-2 inhibitory activity, was remarkable.
Journal of Molecular Structure, Aug 1, 2023
Bioorganic & medicinal chemistry, 2014
In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and invest... more In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and investigated their activity for inhibition of cell proliferation against five human cancer cell lines (HeLa, MCF7, MDA-MB-231, Raji and HL-60) by MTT assay. Compound 3e showed significant antiproliferative activity against both the Raji and HL-60 cell lines with IC50 values of 9.5 and 5.1 μM, respectively. Compound 3e also exhibited moderate inhibitory activity on tubulin polymerization (IC50=17 μM). Flow cytometric analysis of cultured cells treated with 3e also demonstrated that the compound caused cell cycle arrest at the G2/M phase in HL-60 and HeLa cells. Moreover, 3e, the most active compound, caused an apoptotic cell death through the activation of caspase-3. Docking simulations suggested that 3e binds to the colchicine site of tubulin.
Research Square (Research Square), Jun 19, 2020
Current Pharmaceutical Design, 2023
: Hepatocellular carcinoma (HCC) is one of the foremost causes of tumor-affiliated demises global... more : Hepatocellular carcinoma (HCC) is one of the foremost causes of tumor-affiliated demises globally. The HCC treatment has undergone numerous developments in terms of both drug and non-drug treatments. The United States Food and Drug Administration (FDA) has authorized the usage of a variety of drugs for the treatment of HCC in recent years, involving multi-kinase inhibitors (lenvatinib, regorafenib, ramucirumab, and cabozantinib), immune checkpoint inhibitors (ICIs) (pembrolizumab and nivolumab), and combination therapies like atezolizumab along with bevacizumab. There are currently over a thousand ongoing clinical and preclinical studies for novel HCC drugs, which portrays a competent setting in the field. This review discusses the i. FDA-approved HCC drugs, their molecular targets, safety profiles, and potential disadvantages; ii. The intrial agents/drugs, their molecular targets, and possible benefits compared to alternatives, and iii. The current and future status of potential preclinical drugs with novel therapeutic targets for HCC. Consequently, existing drug treatments and novel strategies with their balanced consumption could ensure a promising future for a universal remedy of HCC in the near future.
Chemistry & Biodiversity, Apr 14, 2021
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Japanese Journal of Cancer Research, 2002
Previous experiments have shown that emodin is highly active in suppressing the proliferation of ... more Previous experiments have shown that emodin is highly active in suppressing the proliferation of several tumor cell lines. However, it is not clear that emodin can induce growth inhibition of hepatoma cells. We have found that emodin induces apoptotic responses in the human hepatocellular carcinoma cell lines (HCC) Mahlavu, PLC/PRF/5 and HepG2. The addition of emodin to these three cell lines led to inhibition of growth in a time-and dose-dependent manner. Emodin generated reactive oxygen species (ROS) in these cells which brought about a reduction of the intracellular mitochondrial transmembrane potential (∆ ∆ ∆ ∆ψ ψ ψ ψ m), followed by the activation of caspase-9 and caspase-3, leading to DNA fragmentation and apoptosis. Our findings demonstrate that ROS and the resulting oxidative stress play a pivotal role in apoptosis. Preincubation of hepatoma cell lines with the hydrogen peroxide-scavenging enzyme, catalase (CAT) and cyclosporin A (CsA), partially inhibited apoptosis. These results demonstrate that enhancement of generation of ROS, ∆ ∆ ∆ ∆ψ ψ ψ ψ m disruption and caspase activation may be involved in the apoptotic pathway induced by emodin.
Additional file 1. The chemical properites of 5b-5u compounds. Figure S1-S23: Chemical structure,... more Additional file 1. The chemical properites of 5b-5u compounds. Figure S1-S23: Chemical structure, NMR and IR spectrums of all syntheszied compounds. Table S1: IC50 values (μM) of selected compounds on immortalized normal human epithelial breast cell line, MCF12A. Figure S24. Full images of blots represented in Figure 3B and 4C. Images are obtained with Odyssey® CLx instrument using 700 nm (red) or 800 nm (green) channels.
Bioorganic & Medicinal Chemistry, 2014
In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and invest... more In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and investigated their activity for inhibition of cell proliferation against five human cancer cell lines (HeLa, MCF7, MDA-MB-231, Raji and HL-60) by MTT assay. Compound 3e showed significant antiproliferative activity against both the Raji and HL-60 cell lines with IC 50 values of 9.5 and 5.1 µM, respectively. Compound 3e also exhibited moderate inhibitory activity on tubulin polymerization (IC 50 = 17 µM). Flow cytometric analysis of cultured cells treated with 3e also demonstrated that the compound caused cell cycle arrest at the G2/M phase in HL-60 and HeLa cells. Moreover, 3e, the most active compound, caused an apoptotic cell death through the activation of caspase-3. Docking simulations suggested that 3e binds to the colchicine site of tubulin.
Nature Communications
Complex carbohydrates (glycans) are major players in all organisms due to their structural, energ... more Complex carbohydrates (glycans) are major players in all organisms due to their structural, energy, and communication roles. This last essential role involves interacting and/or signaling through a plethora of glycan-binding proteins. The design and synthesis of glycans as potential drug candidates that selectively alter or perturb metabolic processes is challenging. Here we describe the first reported sulfur-linked polysaccharides with potentially altered conformational state(s) that are recalcitrant to digestion by heparanase, an enzyme important in human health and disease. An artificial sugar donor with a sulfhydryl functionality is synthesized and enzymatically incorporated into polysaccharide chains utilizing heparosan synthase. Used alone, this donor adds a single thio-sugar onto the termini of nascent chains. Surprisingly, in chain co-polymerization reactions with a second donor, this thiol-terminated heparosan also serves as an acceptor to form an unnatural thio-glycosidic ...
Turkish Journal of Chemistry
A series of 4-benzyl/phenyl-3-(1-methyl-1 H-indole-2-yl)-1 H-1,2,4-triazole-5(4 H)-thione (4a,b) ... more A series of 4-benzyl/phenyl-3-(1-methyl-1 H-indole-2-yl)-1 H-1,2,4-triazole-5(4 H)-thione (4a,b) and 2-{4-[benzyl/phenyl-5-(substitutedbenzylthio)]-4 H-1,2,4-triazole-3-yl}-1-methyl-1 H-indole derivatives (5a-p) were synthesized and evaluated for their in vitro scavenging of DPPH and superoxide radical, and lipid peroxidation inhibition effects as well as their antimicrobial properties. DPPH radical scavenging capacity was found to be equipotent with BHT and found in compounds containing 1,2,4-triazole-5(4 H)-thione moiety (4a,b). With regard to antimicrobial properties, compound 5k showed slight antimicrobial activity against all the test microorganisms.
BMC Chemistry
Background Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth le... more Background Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, 1H-NMR and 13C-NMR spectroscopy and element analysis. Results The cytotoxic activity was performed against Huh7, MCF7 and HCT116 cancer cell lines using sulforhodamine B assay. Some compounds showed potent anticancer activities and three of them were chosen for further evaluation on liver cancer cell lines based on SRB assay and real-time cell growth tracking analysis. Compounds were shown to cause arrest in the G0/G1 phase in Huh7 cells and caused a significant decrease in CDK4 levels. A good correlation was obtained between the theoretical predictions of bioavailability using Molinspiration calculation, Li...
Drug Discovery Today, 2022
Breast cancer (BC), the second leading cause of cancer-related deaths after lung cancer, is the m... more Breast cancer (BC), the second leading cause of cancer-related deaths after lung cancer, is the most common cancer type among women worldwide. BC comprises multiple subtypes based on molecular properties. Depending on the type of BC, hormone therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Several new molecular targets, miRNAs, and long non-coding RNAs (lncRNAs), have been discovered over the past few decades and are powerful potential therapeutic targets. Here, we review advanced therapeutics as new players in BC management.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Current Medicinal Chemistry, 2022
: Cancer is one of the leading causes of fatality and mortality worldwide. Investigations on deve... more : Cancer is one of the leading causes of fatality and mortality worldwide. Investigations on developing therapeutic strategies for cancer are supported throughout the world. The massive achievements in molecular sciences involving biochemistry, molecular chemistry, medicine, and pharmacy, and high throughput techniques such as genomics and proteomics have helped create new potential drug targets for cancer treatment. Microtubules are very attractive targets for cancer therapy because of the crucial roles they play in cell division. In recent years, lots of efforts have been put into the identification of new microtubule-targeting agents (MTAs) in anticancer therapy. Combretastatin A-4 (CA-4) is a natural compound that binds to microtubules’ colchicine binding site and inhibits microtubule polymerization. Due to CA-4’s structural simplicity, many analogs have been synthesized. This article summarises the new molecule development efforts to reach CA-4 analogues by pharmacophore group modifications, which have been reported since 2015.
Journal of Molecular Structure, 2022
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Papers by Sultan Nacak Baytas