scholarly journals Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

2019 ◽  
Vol 10 (1) ◽  
pp. 229
Author(s):  
Gergő Mótyán ◽  
Ádám Baji ◽  
Małgorzata Anna Marć ◽  
Mohana Krishna Gopisetty ◽  
Dóra I. Adamecz ◽  
...  
Keyword(s):  
Human Cancer ◽  
Condensation Reaction ◽  
Microwave Assisted Synthesis ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Microwave Assisted ◽  
Proton Dissociation ◽  
Ic50 Values ◽  
Spectrophotometric Titrations

Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of the products depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8–4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

scholarly journals Synthesis and screening of anticancer potentials of some new terephthaldehyde-derived nitrone compounds

2020 ◽  
Vol 19 (2) ◽  
pp. 341-349
Author(s):  
Husam Hamza Salman ◽  
Munther Abduljaleel Mohammed Ali ◽  
Eman Tariq Ali
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Condensation Reaction ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Anticancer Properties ◽  
Chemical Structures ◽  
Ic50 Values ◽  
Mcf 7

Purpose: To synthesize and screen some new nitrone compounds derived from terephthaldehyde for their anticancer potential. Methods: Six new compounds (H, p-Me,p-Br, p-Cl, o-Cl and m-Me) were synthesized via a condensation reaction between terephthaldehyde and a variety of aryl hydroxylamine compounds derived from nitrobenzene and its derivatives. The chemical structures of these compounds were identified using elemental CHN analysis and were elucidated using Fourier Transform infra-red (FT-IR), 1H-nuclear magnetic resonance (1H NMR), mass spectrometry (MS), and elemental analysis. The anticancer effects of the compounds were screened in vitro with respect to their cytotoxicity on MCF7 human cancer cells line. The IC50 values were obtained by MTT assay and their effects on apoptosis of MCF-7 cells were assessed using Acridine orange-ethidium bromide AO/EtBr staining method under a fluorescence microscope. Results: Only four compounds (2b, 2d, 2e, and 2f) inhibited more than 50 % of the growth of MCF-7 cells. The strongest anti-proliferation effect against MCF-7 cells was exhibited by 2f (m-Me), producing more apoptosis which increased membrane disruption and consistency of lysosome vacuoles; it also exhibited higher cytotoxic effects on human cancer cell lines (IC50 < 7.5) than the other synthesized compounds. Conclusion: The new nitrone compounds (2b, 2d, 2e, and 2f) synthesized from terephthaldehyde exhibit some anticancer properties, and so are potential anticancer agents. Keywords: Terephthaldehyde, Nitrone, Cytotoxicity, Anticancer, MCF-7 cells

scholarly journals Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 656
Author(s):  
Rubina Munir ◽  
Muhammad Zia-ur-Rehman ◽  
Shahzad Murtaza ◽  
Sumera Zaib ◽  
Noman Javid ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Public Health Problem ◽  
Microwave Assisted Synthesis ◽  
Major Public Health Problem ◽  
Spectroscopic Techniques ◽  
Dual Inhibitor ◽  
Microwave Assisted ◽  
Ic50 Values

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC50 values less than 20 μM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC50 values of 9.68 and 11.59 μM, respectively. Various informative structure–activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties.

Microwave-assisted Single Step Cinnamic Acid Derivatization and Evaluation for Cytotoxic Potential

2020 ◽  
Vol 21 (3) ◽  
pp. 236-243
Author(s):  
Sonali Mishra ◽  
Shilpi Singh ◽  
Arif Ali ◽  
Amit C. Gupta ◽  
Karuna Shanker ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cinnamic Acid ◽  
Human Cancer ◽  
Single Step ◽  
Breast Adenocarcinoma ◽  
Microwave Assisted Synthesis ◽  
Hek 293 ◽  
Anticancer Properties ◽  
Microwave Assisted

Background: Phenylpropylene biosynthesis pathway plays a crucial role in the vanillin and their derivative(s) production in the plants. The intermediate of vanillin synthesis i.e. cinnamic acid (CA) is converted into 2-Hydroxy 4-MethoxyBenzaldehyde (HMB) in Decalepis arayalpathra having a number of therapeutic value. Objective : Microwave-assisted modifications in cinnamic acid were planned for potential anticancer properties with better yield and efficiency. The present study also confirms the presence of HMB and its precursor i.e. cinnamic acid in D. arayalpathra tubers. Methods: We used a single step Microwave Assisted Synthesis (MAS) to modify cinnamic acid, and then examined the synthetic and natural cinnamic acid derivatives anticancer potential against six human cancer (K-562, WRL-68, A549, A431, MCF-7, and COLO-201) and two normal (L-132 and HEK-293) cell lines at 2, 10 and 50 µg/ml concentrations. Results: β-bromostyrene and β -nitrostyrene have shown inhibition with IC50 values ranging 0.10-21 µM and 0.03-0.06 µM, respectively to the cancer cell lines. β-bromostyrene was the most potent anticancer derivative of CA with better cellular safety and biocompatibility. Conclusions: The present study of microwave-assisted synthesis demonstrates a single-step modification in cinnamic acid. MAS is a fast, reliable, and robust method. The resultant compounds have shown in-vitro anticancer activity against human lung carcinoma and breast adenocarcinoma.

In vitro biological activity of synthesized silver nanoparticles using Myrtus extract

NanoNEXT ◽  
2021 ◽  
pp. 8-19
Author(s):  
Neda Mohamadi ◽  
Mohsen Doostmohammadi ◽  
Iraj Sharifi ◽  
Mehdi Bamorovat ◽  
Ahmad Khosravi ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cell Lines ◽  
Human Cancer ◽  
Negative Control ◽  
Ros Production ◽  
Bacterial Cells ◽  
Human Cancer Cells ◽  
Ic50 Values ◽  
Mcf 7

This study aimed to synthesize and characterize silver nanoparticles (AgNPs) from M. communis laves, and determine their potential activity against human cancer cells as well as leishmanial and bacterial cells. The UV-visible spectroscopy showed an absorption peak at 430 nm wavelengths which is one of the characteristic features of AgNPs. The FESEM image showed irregular shape with a size range of 20-70 nm. MTT results in A172 and MCF-7 cell lines exposed to 5-240 g/mL for 48 hours revealed that M. communis-AgNPs were cytotoxic, with IC50 values of 93.2 g/mL for A172 cell lines and 89.1 g/mL for MCF-7 cell lines, respectively. DCFH-DA analysis showed that 24 h exposure to 25- 200 μg/mL concentrations of AgNPs significantly increased ROS production in cells that indicate oxidative stress induction by AgNPs. M. communis-AgNPs showed overexpression of BCL-2 and Bax genes compared with Glucantime®and negative control (p<0.001) as a potent leishmanicidal and bactericidal activity. The primary modes of action seem to be involved by promotion of the ROS production and up-regulation of BCL-2 and Bax against cancer cell lines. As a result, M. communis-AgNPs formulation should be regarded as a promising agent for potential anti-cancer, anti-leishmanial, and anti-bacterial drugs in therapeutic control programs

An Efficient Solvent-Free Microwave-Assisted Synthesis of Cinnamamides by Amidation Reaction Using Phenylboronic Acid/Lewis Base Co-catalytic System

Synthesis ◽  
2019 ◽  
Vol 51 (20) ◽  
pp. 3891-3900 ◽  
Author(s):  
Khadidja Khaldoun ◽  
Abdelmounaim Safer ◽  
Salima Saidi-Besbes ◽  
Bertrand Carboni ◽  
Rémy Le Guével ◽  
...  
Keyword(s):  
Catalytic System ◽  
Human Cancer ◽  
Condensation Reaction ◽  
Phenylboronic Acid ◽  
Solvent Free ◽  
Lewis Base ◽  
Microwave Assisted Synthesis ◽  
Cytotoxic Activities ◽  
Microwave Assisted ◽  
Solvent Free Conditions

A microwave-assisted dehydrative amide condensation reaction is reported as an efficient access to cinnamamide derivatives under solvent-free conditions. This protocol between conjugated carboxylic acids and amines is based on the use of a co-catalytic system, including the presence of the commercially available phenylboronic acid and 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO), with a complete chemoselectivity in favor of the corresponding α,β-unsaturated amides. The implementation of the reaction needs no special precaution, and less reactive amines, such as substituted anilines, are also efficient under these conditions. A series of novel conjugated amides have been evaluated for their cytotoxic activities against several human cancer cell lines.

scholarly journals Gold(III) Pyridine-Benzimidazole Complexes as Aquaglyceroporin Inhibitors and Antiproliferative Agents

Inorganics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 123 ◽  
Author(s):  
Brech Aikman ◽  
Margot Wenzel ◽  
Andreia Mósca ◽  
Andreia de Almeida ◽  
Wim Klooster ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Donor Ligands ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Human Red Blood Cells ◽  
Anticancer Effects ◽  
Protein Isoform ◽  
The Stability

Gold compounds have been proven to be novel and versatile tools for biological applications, including as anticancer agents. Recently, we explored the potential of Au(III) complexes with bi-dentate N-donor ligands as inhibitors of the membrane water and glycerol channels aquaporins (AQPs), involved in different physiological and pathophysiological pathways. Here, eight new Au(III) complexes featuring a pyridine-benzimidazole scaffold have been synthesized and characterized via different methods. The stability of all the compounds in aqueous solution and their reactivity with glutathione have been investigated by UV–visible spectroscopy. The Au(III) compounds, tested for their AQPs inhibition properties in human Red Blood Cells (hRBC), are potent and selective inhibitors of AQP3. Furthermore, the compounds’ antiproliferative effects have been studied in a small panel of human cancer cells expressing AQP3. The complexes show only very moderate anticancer effects in vitro and are mostly active against the melanoma A375 cells, with marked expression of AQP3 at the level of the nuclear membrane. In general, the AQP3 inhibition properties of these complexes hold promises to develop them as chemical probes to study the function of this protein isoform in biological systems.

scholarly journals Microwave-Assisted Synthesis of Schiff Bases of Isoniazid and Evaluation of Their Anti-Proliferative and Antibacterial Activities

Molbank ◽  
10.3390/m1189 ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. M1189
Author(s):  
Bayan Ahed Al-Hiyari ◽  
Ashok K. Shakya ◽  
Rajashri R. Naik ◽  
Sanaa Bardaweel
Keyword(s):  
Antibacterial Activity ◽  
Schiff Bases ◽  
Aromatic Aldehydes ◽  
Antibacterial Activities ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
Ic50 Values ◽  
In Vitro Inhibition ◽  
Mcf 7

Three new Schiff bases of isoniazid were synthesized using microwave-assisted synthesis and conventional condensation with aromatic aldehydes. Synthesized compounds were characterized using elemental analysis, IR, NMR, and Mass spectroscopy. Synthesized compounds were evaluated for antiproliferative activity against MCF-7 cell line. The IC50 values were from 125 to 276 µM. The compounds were also evaluated for antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the synthesized compounds produce significant antibacterial activity in vitro. Inhibition of compounds ranged from 13 to 18 mm.

scholarly journals Potent and selective in vitro and in vivo antiproliferative effects of metal–organic trefoil knots

2019 ◽  
Vol 10 (23) ◽  
pp. 5884-5892 ◽  
Author(s):  
Farah Benyettou ◽  
Thirumurugan Prakasam ◽  
Anjana Ramdas Nair ◽  
Ini-Isabee Witzel ◽  
Marwa Alhashimi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Self Assembly ◽  
Human Cancer ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Metal Organic ◽  
Simple Pair ◽  
Trefoil Knots

A set of metal–organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells––including those resistant to cisplatin––and in zebrafish embryos.

scholarly journals In vitro Antiproliferative Potential of Celtis iguanaea against Ovarian (OVCAR-3) and Colon (HT-29) Tumor Cell

2019 ◽  
pp. 1-9
Author(s):  
Barbara Zanchet ◽  
Daniela Miorando ◽  
Denise Bianchin Gomes ◽  
Gelvani Locateli ◽  
Cristian Alex Dalla Vecchia ◽  
...  
Keyword(s):  
Tumor Cell ◽  
High Selectivity ◽  
Human Cancer ◽  
Hexane Fraction ◽  
Hydroalcoholic Extract ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Urinary Infections ◽  
Ht 29

Natural products have been reported as a main source of anticancer molecules. The species Celtis iguanaea (Jacq.) Sarg., (Cannabaceae) is widely distributed in Brazil where it is known as “esporão-de-galo or taleira”. The leaves are popularly used as anti-inflammatory, in the treatment of body pain and urinary infections. However, the antiproliferative potential against human cancer cells remain to be elucidated. In this study, extracts and different fractions from the leaves of C. iguanaea were tested in vitro, against a panel tumor cell lines. The hydroalcoholic extract was inactive, while dichloromethane extract showed promisor antiproliferative effects. In turn, the dichloromethane fraction showed potent cytostatic activity against ovarian cell line (OVCAR-3, GI50 = 4.65 mg/ml). However, the stronger antiproliferative effects with high selectivity were observed for the hexane fraction that exhibited activity against ovarian (GI50 = 3.99 mg/ml) and colon (HT-29, GI50 = 3.16 mg/ml). The antiproliferative effects observed are probably related to the presence of 3,7,11,15-tetramethyl-2-hexadecen-1-ol and gamma-sitosterol present in the hexane fraction and detected by GC/MS. This is the first report of antiproliferative activity of C. iguanaea and the results suggested that the molecules of fraction hexane are promising chemotherapeutic compounds, especially against tumor cell of ovarian and colon.

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

Sign in / Sign up

Export Citation Format

Share Document