Derivatives 4a-j Research Articles

An Efficient Synthesis of Novel Aminothiazolylacetamido-Substituted 3,5-Bis(arylidene)-4-piperidone Derivatives and Their Cytotoxicity Studies.

The expansion of 3,5-bis(arylidene)-4-piperidone derivatives with heterocyclic compounds such as 1,3-thiazole should take into account this correlation. The synthesized aminothiazolylacetamido-substituted 3,5-bis(arylidene)-4-piperidone derivatives 3a-j were found to have GI50 values in the range of 0.15-0.28 μM against HeLa and HCT116 cancer cell lines. In silico docking studies confirmed that the proteasome inhibition mechanism involves a nucleophilic attack from the N-terminal threonine residue of the β-subunits to the C=O group of compounds. A C=O group of amide was able to interact with the NH group of the alanine residue and the 5g NH group of amino thiazole, along with an OH group of the serine residue. These results strongly suggest that the synthesized compounds could be a potential candidate inhibitor of the 20S proteasome. These molecules have the potential to be developed as cytotoxic and anticancer agents, as revealed by this study.

Computational Studies and Synthesis of New Heterocyclics as CNS Agents.

This research work aimed to design and synthesize some new molecules of phenothiazine. The work's emphasis was on forming new phenothiazines in two series, 1-(10H-phenothiazin- 10-yl)-2-((4-(1-(phenylimino)ethyl)phenyl)amino)ethan-1-one derivatives (4a-4j) and 1-(4-((2-oxo-2- (10H-phenothiazin-10-yl)ethyl)amino)phenyl)-3-phenylprop-2-en-1-one derivatives (P1-P5). Chloroacetylation of phenothiazine was done to afford 2-chloro-1-(10H-phenothiazin-10- yl)ethan-1-one, which was further reacted with 4-amino acetophenone to produce 2-((4- acetylphenyl)amino)-1-(10H-phenothiazin-10-yl)ethan-1-one. Then, it was treated with substituted anilines and substituted benzaldehydes to produce the final derivatives 4a-4j and P1-P5, respectively. All 15 derivatives (4a-4j and P1-P5) were characterized by evaluating their Rf value, melting point, solubility, IR spectroscopy, and 1HNMR spectroscopy. Molecular docking was performed by using AutoDock Vina v.1.2.0 (The Scripps Research Institute, La Jolla, CA, USA) docking software, and the anxiolytic activity of the derivatives was assessed by using the elevated plus maze model. The designed scheme was executed in the departmental laboratory. The chemical structure of the compounds was confirmed on the basis of TLC, IR, and 1HNMR analyses. The docking study revealed a good docking score of the compounds. The Log P value of the compounds indicated their good penetration into CNS. The compounds were also screened for anxiolytic activity. Among them, compounds 4f, 4h, and P3 showed maximum activity as anti-anxiolytic agents.

Design, synthesis, and biological evaluation of some new 2-phenyl-3,6-pyridazinedione derivatives as PDE-5 inhibitors

Various 2-phenyl-3,6-pyridazinedione derivatives 4a-j, 5a-c, 6a,b, 7a-c, 8, 9, 10a-d, and 11a-d, were effectivelysynthesized, and tested for their potential inhibition of phosphodiesterase enzyme at 10 µM. Then fourteen compounds exhibiting the highest inhibition 4b, 4d, 4e, 4g, 4h, 4i, 5a, 6a,b, 7c, 10a,b, 11a, and 11d were selected for screening their PDE-5 inhibition, where compounds 4b,g,h, and 11a revealed promising PDE-5 inhibition having IC50 values = 25, 53, 22, and 42 nM, respectively in comparison with Sildenafil (IC50 = 16 nM). Additionally, these four most active compounds were safe to normal fibroblast cell line WI-38. Moreover, 4f, 4h, 4j, 10d, and 11d had almost the same anti-proliferative effect against the aortic cell line as Sildenafil. Furthermore, molecular docking illustrated that the binding of the target compounds with the key amino acids in the binding site of PDE-5 (PDB 2H42) was like to that of the cocrystallized ligand Sildenafil. Additionally, molecular dynamics simulation for the most active compound 4h revealed high stability of the 4h -PDE5 complex explaining its promising activity as a PDE-5 inhibitor. Therefore, the 2-phenyl-3,6-pyridazinedione scaffold can be considered an important core for designing more promising PDE-5 inhibitors.

Synthesis of new pyrazolidines by [3+2] cycloaddition: Anticancer, antioxidant activities, and molecular docking studies

A series of novel pyrazolidine derivatives 2a-j from N-acyl hydrazones 1a-j were designed and synthesized by N-triflylphosphoramide (NTPA) catalyzed [3 + 2] cycloaddition. The structural elucidation of synthesized compounds was carried out using a variety of spectroscopic methods, including IR, 1H and 13C NMR, MS, and elemental analysis. Cytotoxic activity of the pyrazolidine derivatives 2a-j was evaluated against human lung cancer (A549), pancreatic cancer (PANC 1), prostate cancer (DU-145), breast cancer (MCF-7), and in human dermal fibroblast (HDF) by MTS assay. The compounds 2f (IC50= 12.5 μM) and 2g (IC50= 21.8 μM) showed higher antiproliferative activity than all other compounds against the A549 human lung cancer line and PANC1 pancreatic cancer line, respectively. The antioxidant potential of the new pyrazolidines 2a-j was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. Compounds 2a, 2d, and 2j were found to exhibit significant antioxidant activity compared to standards. Through molecular docking studies, the antiproliferative properties of the novel pyrazolidine compounds 2a–j were studied, and the interactions between the ligand and the protein were determined for the most active compounds, 2f and 2g.

Synthesis of 1-Halophenyl-pyrazolophthalazine derivatives and evaluation of their antimicrobial activity.

Multi-component reactions for the preparation of pyrazolophthalazine derivatives under microwave irradiation from different aromatic aldehydes with a mixture malononitrile and phthalhydrazide derivatives were established. The antimicrobial activity of the target compounds was evaluated against four bacteria and two fungi using standard antibiotics Ampicillin and mycostatine as reference drugs. The structure-activity relationship studies reported that the substitution at 2,4, and 2,5-positions in the 1H-pyrazolo nucleus with the specific halogen atom increases the ability of the molecule against the antimicrobial activity. The structures of the synthesized compounds were established based on spectral data, IR, 1H NMR, 13C NMR and MS data. Design a series of new pyrazolophthalazine moieties and study the antimicrobial activity of these compounds Materials and Methods: pyrazolophthalazine derivatives 4a-j were synthesized by reaction of phthalhydrazide (1) with malononitrile (2), and various halogen aromatic aldehydes 3a-j in and EtOH/ Pip. Solution under microwave irradiation settings for two minutes at 140 °C Results: In this study, the antimicrobial activity of the synthesized compounds 4a-j was examined for their in vitro antimicrobial activity by using the agar diffusion method using Mueller-Hinton agar medium for bacteria and Sabouraud's agar medium for fungi. Ampicillin and mycostatine were included in the experiments as reference drugs. A series of new pyrazolophthalazine derivatives were synthesized in this work. All compounds were evaluated for antimicrobial activity.

Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors.

A series of N-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids 2a-j and thioacetyl-linked ciprofloxacin-pyrimidine hybrids 5a-i were synthesized. The target compounds were investigated for their antibacterial activity against S. aureus, P. aeruginosa, E. coli, and C. albicans strains, respectively. Ciprofloxacin derivatives 2a-j and 5a-i revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06-42.23µg/mL compared to ciprofloxacin with an MIC range of 0.15-3.25µg/mL. Among the tested compounds, hybrids 2b, 2c, 5a, 5b, 5h, and 5i exhibited remarkable antibacterial activity with MIC range of 0.06-1.53µg/mL against the tested bacterial strains. On the other hand, compounds 2c, 2e, 5c, and 5e showed comparable antifungal activity to ketoconazole against candida albicans with MIC range of 2.03-3.89µg/mL and 2.6µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC50 range of 0.231 ± 0.01-7.592 ± 0.40µM and 0.323 ± 0.02µM, respectively. Docking studies of compounds 2b, 2c, 5b, 5c, 5e, 5h, and 5i on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin.

Synthesis Characterization and Antibacterial Activity of 4-Ethynyl Chalcone Derivatives

Chalcones are polyhydroxylated aryl rings with most of their biological importance. The chemistry of chalcones remained fascinating among researchers due to their simple chemistry, ease of synthesis, large number of replaceable hydrogens and variety of pharmacological activities. In this present investigation our aim is to synthesize a set of 4-ethynylchalcones (3a-j) and to evaluate their Anti-bacterial activity. Synthesis of chalcone derivatives 3a-j was achieved using the classical Claisen- Schmidt reaction. The synthesized chalcone derivatives (3a-j) were tested against Gram negative strains of (i) Escherichia coli (MTCC 443) and (ii) Pseudomonas aeruginosa (MTCC 424) and Gram-positive strains of (iii) Staphylococcus aureus (MTCC 96) and (iv) Streptococcus pyogenes (MTCC 442) using agar well diffusion method. The compounds were dissolved in dimethyl sulphoxide (DMSO) to obtain solutions of concentration 250 μg mL-1. Ciprofloxacin was used as the reference antibacterial drug. Yields of the chalcone derivatives differed from 70 to 85%. The structures of newly synthesized chalcone derivatives 3a-j were established by spectroscopic techniques like 1H NMR, mass and IR spectra of the chalcone derivatives 3a-j are in agreement with the desired structures. Chalcone derivatives (3a-j) characterized by Infrared, ESI-Mass and NMR spectroscopy. Chalcones (3b, 3g, 3h and 3j) with R = 4-OMe, 3-OH, 3-CN and 3,4,5-OMe exhibit good antibacterial activity, the chalcones (3e and 3f) with R = H and 3-NO2 show moderate antibacterial activity and the remaining chalcones in the series such as 3a, 3c, 3d and 3i with R = 4-Br, 3-Br, (3-Br, 4-F) and 4-CH3 display weak antibacterial activity against tested bacterial strains. Now a days health care became a more necessity thing in every one life. So, these chalcone derivatives are may helpful in development of less side effect radical quenching drugs.

Synthesis of Novel Amide and Schiff’s Base Functionalized Novel Pyrido[ 1,2-a] Pyrimidin-4-One Derivatives and Their Anticancer Activity Studies

Abstract:A series of novel amide and Schiffs base functionalized novel pyrido[1,2-a] pyrimidin- 4-one derivatives was prepared starting from 6-(thiophen-2-yl)/phenyl-4-(trifluoromethyl) pyridin- 2-amine 1a and 1b. These compounds on reacting with EMME afford compounds 2a and 2b, followed by cyclization to afford compounds 3a and 3b. Treatment of compounds 3a and 3b with hydrazine hydrate gave compounds 4a and 4b, which further reacted with different substituted aromatic aldehydes to give Schiff’s base derivatives 5a-j. In another way, compounds 3a, 3b by reacting with aliphatic amines give amide derivatives 6a-f. All the compounds, 5a-j and 6a-f, were screened against four human cancer cell lines (HeLa, COLO205, Hep G2, and MCF 7). Among all the derivatives, compounds 5c, 5e, 6a, and 6b showed promising anticancer activity.

Synthesis, characterization, and antimicrobial activity of some thiazole derivatives

Thiazole derivatives 2a-c were synthesized via reaction of 2-chloro-N-phenylacetamide (1) and thiourea, thiosemicarbazide or thioacetamide in alcoholic potassium hydroxide. Also, substituted benzaldehyde reacted with thiosemicarbazide at reflux temperature in ethanol to afford hydrazone compounds 3a-k. Under microwave irradiation (M.I., 100W) with neat for 20sec; arylketones, thiosemicarbazide and chloroacetylchloride were reacted to afford thiazole derivatives 4a-j. Compounds are characterized by physical measurements, NMR and infrared spectra. Antibacterial activity of new compounds was evaluated with Gram Negative Serratia marcesence, Proteus vulgaris, Escherichia coli and Psudomonas aeruginosa and Gram Positive; Staphylococcus aureus in comparison with Norfloxacin and Ciprofloxacin as standard drugs.

Synthesis, Antifungal Activity, DFT Study and Molecular Dynamics Simulation of Novel 4‐(1,2,4‐Oxadiazol‐3‐yl)‐N‐(4‐phenoxyphenyl)benzamide Derivatives

In order to find novel potential antifungal agrochemicals, a series of new 4-(1,2,4-oxadiazol-3-yl)-N-(4-phenoxyphenyl)benzamide derivatives 3a-j were designed, synthesized and characterized by their 1 H-, 13 C-NMR and HRMS spectra. The preliminary antifungal assay in vitro revealed that compounds 3a-j exhibited moderate to good antifungal activity against five plant pathogenic fungi. Especially, compound 3e presented significant antifungal activity against Alternaria solani, Botrytis cinerea and Sclerotinia sclerotiorum, superior to positive control boscalid. In the in vivo antifungal assay on tomato plants and cucumber leaves, compound 3e presented good inhibition rate against B. cinerea at 200 mg/L. Molecular dynamics simulation revealed that compound 3e could bind with the active site of class II histone deacetylase (HDAC).

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors.

Microtubules and the mitotic spindle have become an important target for cancer treatment due to their critical role in cell division. In this work, a novel series of benzofuran and indole derivatives were designed and synthesized, to be evaluated as tubulin polymerization inhibitors. 2-Acetylbenzofuran derivatives 1a,b and 3-acetylindole 1c were condensed with Wittig reagents 2a-d and Wittig-Horner reagents 3a-e to afford the respective 2-ethylidene derivatives 5a-j and 7a-e. Also, iminomethylene triphenylphosphine (2e) reacted with 1a,b to afford benzofuran-2-ylethylidene aniline derivatives 6a,b. In addition, compounds 1a,b reacted with trialkylphosphites 4a-c to give 1:1 adduct for which the Oxaphospholo[4,3-b]benzofuran-7-yl)diazene derivatives 8a-f, were assigned. The possible reactions mechanisms were discussed and structural reasoning for the new compounds were based upon spectroscopic data. Their antiproliferative activities against two cell lines namely, HepG2 and MCF7 cells were then evaluated. It was found that the benzofuran compounds 5b, 6a, and 8c exhibited the strongest antiproliferative activities against both cell lines compared to doxorubicin. By studying the mechanism of action, compound 6a showed good inhibition of tubulin polymerization which leads to mitotic spindle formation disruption, cell cycle arrest in the G2/M phase, and apoptosis of HepG2 cells. A conducted docking study confirmed the in vitro results indicating that compound 6a fitted properly at the colchicine binding site of tubulin. Based on these findings, compound 6a can be considered as a promising anticancer candidate that can be subjected for further development as a tubulin polymerization inhibitor for treating liver and breast cell carcinoma.

Novel pyrano-triazolo-pyrimidine derivatives as anti- α-amylase agents: Synthesis, molecular docking investigations and computational analysis

A novel series of pyranotriazolopyrimidine derivatives 3a-j was synthesized and characterized by 1H NMR, 13C NMR, and HRMS experimental data. The synthesized compounds were assessed for their inhibitory potential on the α-amylase enzyme. Results showed that seven of the synthesized compounds displayed potent α-amylase inhibitory activity. Compound 3b (IC50 = 2.78 ± 0.14 μg/mL) bearing a cyanomethyl group at triazole ring, exhibited the highest activity followed by 2a, 2b and 3c with IC50 values ranging from 3.15 ± 0.25 to 4.15 ± 0.10 μg/mL, in comparison to the standard acarbose IC50 = 6.84 ± 1.22 μg/mL). A molecular docking study was performed to investigate the possible inhibitory mechanism at the binding site of the target enzyme which reinforced the observed activity of compounds 2a, 2b, 3b, and 3c. The analysis revealed the strength of intermolecular hydrogen bonding and hydrophobic interactions in the ligand-receptor complexes as significant descriptors to rationalize the inhibition results obtained. Several physicochemical properties related to the pharmacokinetics of the synthesized derivatives were predicted. These properties were found to lie within the desired limit and we have noticed that all compounds are likely to be orally active as they obeyed Lipinski's rule of five. HOMO-LUMO energy gap and some reactivity descriptor's parameters were evaluated using Density Functional Theory (DFT) employing B3LYP level with 6-311++G (d,p) basis set.

Design, Synthesis, and Biological Evaluation of 2-(2-Bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole Derivatives as Possible Anti-Breast Cancer Agents.

Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940's. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2-(2-bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4-oxadiazole derivatives 4a-4j have been synthesized and described by spectroscopic method. 2-(2-Bromo-6-nitrophenyl)-5-(4-bromophenyl)-1,3,4-oxadiazole (4c) was reconfirmed by single-crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF-7, MDA-MB-453 and MCF-10A non-cancer cell lines. The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose-dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein-ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.

Synthesis and characterization of 2-benzylidene-1,3-indandione derivatives as in vitro quantification of amyloid fibrils

Timely detection of amyloid aggregations has a critical role in the treatment of degenerative nervous system disorders such as Alzheimer’s, Parkinson’s disease and systemic amyloidosis. Thioflavin T (ThT) is a dye considered for the detection of amyloids. However, ThT cannot cross the blood–barrier barrier due to positive charge and low lipophilicity. In the present study, a variety of 2-benzylidene-1,3-indandione derivatives 5a–5j were synthesized as neutral fluorescence probe candidates for identification of amyloid. Among these compounds, only compound 2-(2-hydroxybenzylidene)-1,3-indandione 5a was selected for further examination, because its fluorescence intensity showed the significant increasing upon interaction with amyloid aggregates. The compound 5a was compared to standard and conventional probe such as ThT. The compound 5a was excited at its specified wavelength, and the fluorescence emission signal was recorded in the presence of different concentrations of the protein/peptide (amyloid aggregated and native protein). According to the obtained results, it can be seen that 2-(2-hydroxybenzylidene)-1,3-indandione 5a selectively and specifically bind to amyloid fibrils, such as ThT. Due to the neutrality of electrical charge and high lipophilicity coefficient of the synthesized compound 5a, it is possible for it to cross from the blood–brain barrier. Our results show that this synthetic derivative can be considered as a suitable probe to detect in vitro amyloid aggregations.

Synthesis and biological evaluation of novel indenopyrazole derivatives

A series of novel indenopyrazole derivatives 2a-j and 3a-j were synthesized from the reaction of 1-(4-(hydroxy(1-oxo-1,3-dihydro-2 H-inden-2-ylidene)methyl)phenyl)-3-phenylurea derivatives 1a-j with hydrazine and phenylhydrazine, respectively. The obtained novel indenopyrazoles ( 2a-j and 3a-j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay; 2a, 2b, 2d, 2h, and 3h were found to be the most active compounds. The compounds were also screened for antimicrobial activity, and all compounds showed moderate activity against used microorganisms.

Synthesis, spectral characterization, docking studies and biological activity of urea, thiourea, sulfonamide and carbamate derivatives of imatinib intermediate.

A series of new urea/thiourea derivatives 3a-j were synthesized by simple addition reaction of functionalized phenyl isocyanates/isothiocyanates 2a-j with N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine (imatinib intermediate) (1) in the presence of 1,4-dimethyl piperazine (DMPZ) as a base, and another series of new sulfonamide/carbamate derivatives 5a-k were synthesized by reacting 1 with various substituted aromatic sulfonyl chlorides 4a-f and aromatic/aliphatic chloroformates 4g-k in the presence of DMPZ as a base. The title compounds 3a-j and 5a-k were characterized by IR, 1H, 13C NMR and mass spectral data. Antimicrobial, antioxidant and in silico molecular docking studies were made against aromatase.

Synthesis of sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors, pharmacokinetic properties, lead optimization, Lineweaver-Burk plot evaluation and binding analysis

To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containing moieties. A new series (4a–4j) of sulfadiazine derived acyl/aryl thioureas was synthesized and characterized through spectroscopic and elemental analysis. The synthesized derivatives 4a–4j were subjected to calf intestinal alkaline phosphatase (CIAP) activity. The derivative 4a–4j showed better inhibition potential compared to standard monopotassium phosphate (MKP). The compound 4c exhibited higher potential in the series with IC50 0.251 ± 0.012 µM (standard KH2PO4 4.317 ± 0.201 µM). Lineweaver-Burk plots revealed that most potent derivative 4c inhibition CIAP via mixed type pathway. Pharmacological investigations showed that synthesized compounds 4a–4j obey Lipinsk’s rule. ADMET parameters evaluation predicted that these molecule show significant lead like properties with minimum possible toxicity and can serve as templates in drug designing. The synthetic compounds show none mutagenic and irritant behavior. Molecular docking analysis showed that compound 4c interacts with Asp273, His317 and Arg166 amino acid residues.

Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors.

The present article illustrated the synthesis and characterization of a novel series of (E)-4-(substituted-benzylideneamino)-2H-chromen-2-one derivatives 4A-4J: in good to excellent yields. The target compounds were synthesized by refluxing 4-aminocoumarin with aromatic aldehydes in ethanol. The structural confirmation was achieved by spectroscopic techniques such as (1H, 13C-NMR and FT-IR) and elemental analysis. The synthesized compounds were evaluated for carbonic anhydrase II (CA-II) inhibition and free radical scavenging activity. All the compounds showed CA-II inhibition in the micro molar range. The compound 4C: exhibited higher potential in the series with IC50=0.0928±0.00545 µM (standard Acetazolamide IC50=0.997±0.0586 µM). Pharmacological investigations showed that the synthesized compounds 4A-4J: obey Lipinsk's rule. Compound 4C: elicited drug likeness and showed drug score value of 0.05. Molecular docking analysis showed that compound 4C: interacts with Asn66 and Gln91 amino acid residues. Graphical Abstract.

Synthesis and Biological Evaluation of Novel 1-(4-(Hydroxy(1-oxo-1,3-dihydro-2H-inden-2-ylidene)methyl)phenyl)-3-phenylurea Derivatives.

A series of novel phenylurea containing 2-benzoylindan-1-one derivatives 3a-3j were synthesized from the reaction of phenylurea-substituted acetophenones 1a-1j with phthalaldehyde 2 under mild reaction conditions in good yields. All synthesized compounds were characterized by spectroscopic methods. The obtained compounds (3a-3j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay, 3f and 3g were found to be most active compounds. The compounds were also screened for antimicrobial activity and all compounds showed remarkable activity against used microorganisms.

Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: Synthesis, characterization and anticancer activity

Cancer treatment still requires new compounds to be discovered. Chalcone and its derivatives exhibit anticancer potential in different cancer cells. A new series of benzofuran substituted chalcone derivatives was synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(7-ethoxy-1-benzofuran-2-yl) ethanone with different aromatic aldehydes to yield 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives 3a-j. The derivatives were characterized by elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy techniques. The anti-growth effect of chalcone compounds was tested in breast cancer (MCF-7), non-small cell lung cancer (A549) and prostate cancer (PC-3) cell lines by the SRB and ATP cell viability assays. Apoptosis was detected by mitochondrial membrane potential, Annexin V staining and caspase 3/7 activity. Formation of reactive oxygen species was determined by DCFDA. The results revealed that chalcone derivatives have anticancer activity with especially chalcone derivative 3a showing cytotoxic effects on cancer cells. In addition, chalcone derivative 3a induced apoptosis through caspase dependent pathways in prostate, lung and breast cancer cells.