Chemistry Commons^™

Quercetin As An Anticancer Candidate For Glioblastoma Multiforme By Targeting Akt1, Mmp9, Abcb1, And Vegfa: An In Silico Study, Muhammad Hermawan Widyananda, Setyaki Kevin Pratama, Arif Nur Muhammad Ansori, Yulanda Antonius, Viol Dhea Kharisma, Ahmad Affan Ali Murtadlo, Vikash Jakhmola, Maksim Rebezov, Mars Khayrullin, Marina Derkho, Emdad Ullah, Raden Joko Kuncoroningrat Susilo, Suhailah Hayaza, Alexander Patera Nugraha, Annise Proboningrat, Amaq Fadholly, Mada Triandala Sibero, Rahadian Zainul

Karbala International Journal of Modern Science

Quercetin, a natural compound present in various fruits and vegetables, shows promise as a potential inhibitor for glioblastoma multiforme (GBM) development. This study aims to examine the anti-GBM potential of Quercetin. The protein target of Quercetin is identified and analyzed using databases such as NCBI, SEA, CTD, and STRING. Protein-protein interaction (PPI) and functional annotation are carried out based on the obtained target proteins. Molecular docking and dynamics simulations are employed using AutoDock Vina and WebGro tools to analyze the interaction between Quercetin and its target proteins. The prediction of protein targets reveals that Quercetin directly targets four proteins associated …

Development Of Novel Cellular Assay Model And Therapeutic Deep Eutectic Solvents To Optimize The Activity Of Anticancer Agents, Nizam Uddin

Electronic Theses and Dissertations

Multidrug resistance (MDR) is the major burden behind chemotherapeutic treatment failure. It is the principal mechanism by which cancer cells evade chemotherapeutic treatment. As a result, aggressive cancer cells survive and continue uncontrolled cell division. Multidrug resistance affects survival rate of almost all types of cancer patients and death toll rises at an alarming rate. There are seven different mechanisms for evolving MDR. The most common mechanism in efflux activity of overexpressed ABC transporters. MRP1 is a prominent ABC transporter that pumps out a wide variety of anticancer drugs from the cells and thereby reduces intracellular drug concentrations and develops …

Molecular Characterization Of Wild Pleurotus Ostreatus (Mw457626) And Evaluation Of Β-Glucans Polysaccharide Activities, Ghazwan Q. Hasan Ph.D., Shimal Y. Abdulhadi Ph.D.

Karbala International Journal of Modern Science

Pleurotus ostreatus is a common cultivated edible mushroom worldwide. The fruiting bodies of P. ostreatus is a rich source of a β-glucans polysaccharide. The current study aimed to investigate the effectiveness of β-glucans as a natural polysaccharide produced by P. ostreatus as an antioxidant, antimicrobial, and anticancer. The molecular identification of P. ostreatus isolate was confirmed by Internal Transcribed Spacer (ITS) sequence. The sequence alignment and phylogenetic evolutionary relationship of studied ITS sequence were performed against some deposited sequences in GenBank. The analysis of high-performance liquid chromatography (HPLC) as well as the result of fourier transform infrared spectroscopy …

Biological Potential Of Copper Complexes: A Review, Jamshaid Ashraf, Muhammad Asad Riaz

Turkish Journal of Chemistry

This review comprises the inorganic compounds particularly metal coordinated complexes, as drugs play a relevant role in medicinal chemistry. It has been observed that copper complexes are potentially attractive as medicinal importance. In this review, the most remarkable achievements of copper complexes undertaken over the past few decades as antimicrobial, antioxidant, enzyme inhibition activity, and anti-cancer agents are discussed. This work was motivated by the observation that no comprehensive surveys of the diversity of biological activities of copper complexes were available in the literature.

Recent Studies On The Synthesis Of Medicinal Molecules., Paige Monsen

Electronic Theses and Dissertations

Medicinal chemistry interfaces synthetic organic chemistry, natural product chemistry and chemical biology, with a goal of yielding therapeutic agents. Natural products or compounds derived from natural sources such as plants, animals, and microorganisms, are often biologically active and render that compound a likely drug lead. For thousands of years humankind has utilized natural products for medicinal purposes and consequently scientists take advantage of both these compounds’ core structural characteristics and their modes of actions on selected targets as inspiration to develop therapeutics. Because the total synthesis of such complex molecules can be cumbersome and expensive, semi-synthetic methods on isolated natural …

Anticancer And Antiangiogenic Activities Of Alkaloids Isolated From Lantana Camara By Adsorption On The Magnetic Nanoparticles, Hussein Kadhem Al-Hakeim, Rahman Sahib Al-Zabibah, Huda Falah Alzihari, Ali Khudhair Almensoori, Hazim A. Al-Zubaidi, Loiy Elsir Ahmed Hassan Hassan

Karbala International Journal of Modern Science

Lantana camara L. (L. camara) is a perennial shrub that contains low amounts of alkaloids. In the present study, the magnetic nanoparticles (MNPs) were used to isolate positively charged alkaloids from the methanolic extract of L. camara leaves. The crude alkaloid was fractionated using HPLC to separate the highest peak of the alkaloid fraction (HPAF). The crude alkaloids (CA) and HPAF were tested for their antiproliferative effect against cancer cell lines (MCF-7, HCT-116, and HeLa) and endothelial cells line (EA.hy926) as a standard cell line. Antiangiogenic properties were examined using rat aortic ring assay. …

Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens

Theses and Dissertations--Chemistry

Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical research and catalytic transformations. Given that auranofin, a gold(I) complex with FDA approval for the treatment of rheumatoid arthritis is used in the clinic, the development of stable gold-based molecules of clinical relevance is urgently needed. Herein are reported, synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented …

Interaction Of A Platinum Triamine Complex Having A Seven-Membered Chelate Ring With N-Acetyl-Lmethionine And Guanosine 5'-Monophosphate, Jae Ko

Masters Theses & Specialist Projects

In the 1960s, Rosenberg and his colleagues confirmed the anti-cancer activity of cisplatin. Although cisplatin was capable of killing testicular cancer cells there were also serious side effects. It was necessary to find alternate ways of overcoming side effects, and soon many researchers have discovered novel platinum compounds that show similar reactivity. Recently, replacing one chloride group to a heterocyclic amine group showed significant cytotoxicity with a different binding activity than cisplatin. Previously in our lab, [Pt(Me5dien)(NO3)]+ and [Pt(Et2dien)Cl]+ have been synthesized and reacted with NAcetyl- L-methionine (N-AcMet) and Guanosine 5’-monophosphate (5’-GMP) showed unusual reactivity. Unlike most previously studied platinum …

Conformational Studies Of Glucose Transporter 1 (Glut1) As An Anticancer Drug Target, Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong

Haizhen Zhong

Glucose transporter 1 (GLUT1) is a facilitative glucose transporter overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. GLUT1 works through conformational switching from an outward-open (OOP) to an inward-open (IOP) conformation passing through an occluded conformation. It is critical to determine which conformation is preferred by bound ligands because the success of structure-based drug design depends on the appropriate starting conformation of the target protein. To find out the most favorable GLUT 1 conformation for ligand binding, we ran systemic molecular docking studies for different conformations of GLUT1 using known …

Conformational Studies Of Glucose Transporter 1 (Glut1) As An Anticancer Drug Target, Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong

Chemistry Faculty Publications

Glucose transporter 1 (GLUT1) is a facilitative glucose transporter overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. GLUT1 works through conformational switching from an outward-open (OOP) to an inward-open (IOP) conformation passing through an occluded conformation. It is critical to determine which conformation is preferred by bound ligands because the success of structure-based drug design depends on the appropriate starting conformation of the target protein. To find out the most favorable GLUT 1 conformation for ligand binding, we ran systemic molecular docking studies for different conformations of GLUT1 using known …

Anticancer And Antiangiogenesis Activities Of Novel Synthesized 2-Substituted Benzimidazoles Molecules, Adem Güner, Eli̇fsu Polatli, Tamer Akkan, Hakan Bektaş, Canan Albay

Turkish Journal of Chemistry

In this study, novel 2-substituted benzimidazoles molecules having triazole, thiadiazole, and oxadiazole rings were synthesized and were evaluated by anticancer, antioxidant/oxidant status, genotoxicity, and antiangiogenesis assays. Anticancer activity of the compounds was determined by MTT (0.5, 5, and 50 $\mu $g/mL) and lactate dehydrogenase (LDH) release assays against human prostate and breast cancer cells. Oxidative status of cells was elicited by total oxidative stress and total antioxidant capacity methods. Chick chorioallantoic membrane assay was used to evaluate the antiangiogenic activity. Genotoxicity was evaluated by the sister chromatid exchange (SCE) and micronucleus (MN) tests in lymphocyte cultured human blood. Our results …

Progress Toward Synthetically Simplified Natural Anticancer Peptide, David W. Kastner, Steven L. Castle

Library/Life Sciences Undergraduate Poster Competition 2018

Yaku’amide A was isolated in late 2010 from the deep-sea sponge Ceratopsion sp. and exhibits potent inhibitory activity against 39 human cancer cell lines via a potentially novel mode of action. However, the total synthesis requires many steps and produces low yields. In this study, we determined two simpler YA analogues that may retain its anticancer properties and can be synthesized in larger quantities. The analogues replace dehydroisoleucine with either dehydroethylnorvaline or dehydrovaline.

Tetrahydropyridine: A Promising Heterocycle For Pharmacologically Active Molecules, Noor Ul Amin Mohsin, Matloob Ahmad

Turkish Journal of Chemistry

The tetrahydropyridine (THP) ring system has received considerable focus due to its excellent ability to act as a pharmacophore. It is recognized as a major constituent in natural alkaloids. THP derivatives have been reported for a diverse range of biological activities. Recent synthetic works contain syntheses of monosubstituted, disubstituted, trisubstituted, highly functionalized, and condensed structures. In this review, we summarize the recent literature dealing with the bioactive nature of this important heterocycle.

A Novel Method For Synthesis Of Hydroxytyrosol, Emmanuel Onobun

Electronic Theses and Dissertations

Hydroxytyrosol, 3,4-dihydroxyphenolethanol, a naturally occurring polyphenol most common in olive tree (Olea europaea), is one of the most effective member of the polyphenols family, because of its remarkable antioxidant activity, its ability to inhibit oxidation of low density lipids (LDL), and its protection against DNA oxidative damage. Hydroxytyrosol, which is widely used in cosmetics and food supplements industries, can be purchased as an olive oil extract that contains low concentration of hydroxytyrosol besides other polyphenols. The price and low natural abundance of hydroxytyrosol make alternative synthetic sources very attractive. In this research, a novel method for the synthesis of pure …

Development Of Dihydrochalcone Functionalized Gold Nanoparticles For Augmented Antineoplastic Activity, Jason N. Payne

Masters Theses & Specialist Projects

Phloridzin, an antidiabetic and antineoplastic agent usually found in fruit trees, is a dihydrochalcone constituent that has a clinical/pharmaceutical significance as a sodiumglucose linked transport 2 (SGLT2) inhibitor. Phloridzin never experienced widespread clinical usage in the pharmaceutical market due to its side effects and poor bioavailability when compared to other antidiabetic therapeutics. The poor bioavailability is primarily attributed to the degradation of the glycosidic bond of the phloridzin, resulting in the formation of phloretin, the aglycone of phloridzin and glucose. While phloretin displays a reduced capacity of SGLT2 inhibition, this nutraceutical shows enhanced antineoplastic activity in comparison to phloridzin. Gold …

Synthesis, Structure-Activity Relationship Study, And Mode Of Action Study Of 1,4-Naphthoquinone Based Anticancer And Antimicrobial Agents, Jaya P. Shrestha

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The first three projects involve the synthesis and the mode of action study of 1,4-naphthoquinone based anticancer agents. These anticancer agents are highly potent against a wide range of cancer cell lines. These compounds showed ~8-fold selectivity towards the lung cancer cell line than the normal cell line. We also studied the mode of action and observed that generation of reactive oxygen species is the primary mode of action.

The final project involves the synthesis of multi-cationic antimicrobial agents. These compounds are active against both bacteria and fungi. These compounds are very easy to synthesize and can be scaled up …

Anticancer, Biophysical And Computational Investigations Of Half-Sandwich Ruthenium(Ii) Thiosemicarbazone Complexes: The Effect Of Arene Versus Thiacrown Face-Cap, Floyd A. Beckford, Alyssa Stott, P. Canisius Mbarushimana, Marc-Andre Leblanc, Kinsey Hall, Samantha Smith, Jimmie L. Bullock, Dennis J. Houghton, Alvin A. Holder, Nikolay Gerasimchuk, Antonio Gonzalez-Sarrías

Chemistry & Biochemistry Faculty Publications

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h⁶-p-cymene)Ru(dmabTSC)Cl]PF₆, [(h⁶-benzene)Ru(dmabTSC)Cl]PF₆ (arene complexes), and [([9]aneS₃(dmabTSC)Cl]PF₆ (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 10 …

Synthesis Of New Platinum-Based Anti-Cancer Drugs, Saud O. Albaroodi Yasser

Masters Theses

Cancer is considered the second leading cause of death after heart attack. Different treatments have been applied to kill cancer cells such as chemotherapy, which is the use of chemicals or drugs in order to treat cancer cells. Platinum-based anti cancer drugs are the backbone of chemotherapy, they play a crucial role in treating various malignant tumor. However, the disadvantages of these drugs are very painful on patients, such as nephrotoxicity and ototoxicity. In the last four decades, thousands of platinum-based anticancer drugs have been synthesized for hope in find a new drug with higher efficacy and less side effects.In …

Relative Reaction Rates Of The Amino Acids Cysteine, Methionine, And Histidine With Analogs Of The Anti-Cancer Drug Cisplatin, Cynthia A. Tope

Mahurin Honors College Capstone Experience/Thesis Projects

We are studying the reaction of analogs of the anticancer drug cisplatin with amino acids that differ in size and shape. The reaction of cisplatin with proteins likely precedes reaction with DNA in the body, forming a variety of products that may be toxic to the human body. The size and shape of the platinum(II) complexes often affects the rate of reaction with proteins, more so than with DNA. In this study, triamine cisplatin analogs are reacted with the amino acids cysteine, methionine, and histidine simultaneously. These reactions are monitored by NMR spectroscopy. The effect of the bulk of the …

Design And Synthesis Of Bioactive Peptidomimetics, Yaogang Hu

USF Tampa Graduate Theses and Dissertations

Protein-Protein Interactions (PPIs) play a very important role in biological functions and therefore the inhibition of specific Protein-Protein Interactions has a huge therapeutic value. The most successful small molecular PPIs inhibitors do not fit with the prevalent `Rule of Five' drug profile. To overcome the disadvantages of small molecular PPIs inhibitors, peptide based PPIs inhibitors were developed. Herein we describe the development of a new class of peptidomimetics AA-peptides. The AApeptides were designed based on chiral PNA backbone. Substitution of nucleobases yields AApeptides that are resistant to proteolysis and capable of mimicking peptides. Two types of AApeptides were discussed in …

Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan

Mahurin Honors College Capstone Experience/Thesis Projects

We are studying reactions of cisplatin derivatives, which differ in both size and shape, with various amino acids. When reaction with DNA occurs, apoptosis is observed, ideally leading to termination of the cancer. Due to the affinity of cisplatin for sulfur-containing amino acids, reaction with proteins may occur prior to access to the DNA, producing a large array of products, which could potentially be toxic to the human body. Both the size and shape of the platinum complexes often affect the reactions with protein targets more so than with DNA targets. By performing reactions of specific amino acids targets with …

Synthesis And Cytotoxic Activity Of Some 2-(2,3-Dioxo-2,3-Dihydro-1h-Indol-1-Yl)Acetamide Derivatives, Özlem Akgül, Ayşe Hande Tari̇koğullari, Fadi̇me Aydin Köse, Petek Ballar Kirmizibayrak, Mehmet Varol Pabuççuoğlu

Turkish Journal of Chemistry

Isatin, 1H-indoline-2,3-dione, an endogenous compound, is also a synthetically versatile molecule that possesses a diversity of biological activities including anticonvulsant, antibacterial, antifungal, antiviral, anticancer, and cytotoxic properties. Based on the promising cytotoxic activity studies on N-substituted isatin derivatives, a series of 18 derivatives of 2-(2,3-dioxo-2,3-dihydro- 1H-indol-1-yl)-N-phenylacetamide were designed, synthesized, and characterized according to their analytical and spectral data. All of the compounds were evaluated for their cytotoxic activity against MCF7, A549, HeLa, and HEK293 cell lines by real time cell analyzer. Etoposide was used as a standard compound. Briefly, ortho substitutions gave better results compared to meta and para substitutions …

Anticancer Activity And Biophysical Reactivity Of Copper Complexes Of 2-(Benzo[D][1,3]Dioxol-5-Ylmethylene)-N-Alkylhydrazinecarbothioamides, Floyd A. Beckford, Jeffrey Thessing, Alyssa Stott, Alvin A. Holder, Oleg G. Poluektov, Liya Li, Navindra P. Seeram

Faculty Publications

A series of copper complexes were synthesized from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) thiosemicarbazones (RHpTSC where R = H, CH3, C2H5 or C6H5 (Ph)). The complexes show interesting variations in geometry depending on the thiosemicarbazone; a dinuclear complex [Cu(HpTSC)Cl]2, a mononuclear complex [Cu(RHpTSC)2Cl2] (R = CH3 or C2H5) and another mononuclear complex [Cu(PhHpTSC)(PhpTSC)Cl] was generated. The complexes bind in a moderately strong fashion to DNA with binding constants on the order of 10⁴ M^{− 1}. They are also strong binders of human serum albumin with binding constants near 10⁴ M^{− 1}. The complexes show good in vitro …

Chemical Modification And Biological Activity Exploration Of The Natural Product-Gossypol, Juanjuan Yin

All Dissertations

Gossypol is a naturally occurring, highly colored yellow pigment indigenous to the small intercellular pigment glands of the cotton plant genus Gossypium, which is proposed to be part of plant's defense system. Gossypol is characterized by wide contraceptive, antiviral, anticancer and antifungal properties. However, the relatively high toxicity of gossypol precludes its application in medical therapy. For this reason the syntheses and tests of gossypol derivatives, have been tried to enable their application as drugs. In our study, gossypol based methylation, glycosylation and nanoconjugate reactions were explored. The gossypol derivatives were all fully characterized by NMR, MS, FT-IR, UV spectrometry, …

A Synthetic Approach Toward Novel Β-Lactams, Mohamed Hashim

Theses and Dissertations - UTB/UTPA

β-lactam antibiotics which is a class by itself, covers a wide range of antibiotics that includes penicillin, penicillin derivatives, cephalosporins, carbapenems, and any antibiotic agent that contains a 2-azetidinone ring.[2] In recent past research it has been established that β-lactams show therapeutic and anticancer activity with low toxicity. [2] It has also been reported by our lab that N-chrysenyl and N-phenanthrenyl 3-acetoxy-4-aryl-2- azetidinone can exhibit potent selective anticancer activity towards prostate, colon, pancreatic cancer and leukemia at low concentrations, all of this was revealed by means of a structure activity study. [2] The goal of our research is the synthesis …

Design Of Novel Anticancer Drugs Utilizing Busulfan For Optimizing Pharmacological Properties And Pattern Recognition Techniques For Elucidation Of Clinical Efficacy, Ronald Bartzatt

Chemistry Faculty Publications

Chronic myelogenous leukemia (CML) is a disorder in which an excessive number of blood stem cells develop into the white blood cell group called granulocytes. The anticancer drug Busulfan is a cell cycle non-specific alkylating agent which is utilized to maintain white blood cell counts below 15000 cells/microliter. The side effects induced by busulfan are significant and affirms the intimation for new drug constructs. Fifteen analogous compounds were generated from the molecular structure of busulfan . These compounds retain the double methanesulfonate functional groups descriptive of this class of alkylating anticancer drugs. However, the carbon chain substituent separating the methanesulfonate …

Retro Models Of The Cisplatin-Dna Cross-Link With Carrier Ligands Having Sp2 N-Donor Triazine Rings, Vidhi Maheshwari

LSU Doctoral Dissertations

Rapid rotation of guanine base derivatives about Pt–N7 bonds results in fluxional behavior of models of the key DNA intrastrand G–G cross-link leading to anticancer activity of Pt(II) drugs (G = deoxyguanosine). This behavior impedes the characterization of LPtG2 models (L = one bidentate or two cis-unidentate carrier ligands; G = guanine derivative). The objective of this study is to understand the types of conformers formed as L is systematically varied. This work, relevant to Pt(II) anticancer drugs, has evolved from published studies with sp3 N-ligands (e.g., 2,2'-bipiperidine), to C2 symmetrical or unsymmetrical sp2 N-ligands having pyridine and/or triazine rings. …