Chalcone Hybrids Research Articles

Synthesis, Characterization and Antibacterial Activity of Some Novel Pyrido[2,3-b]indole, Morpholine and Chalcone Hybrid Compounds

In present investigation, a novel series of (E)-3-(2-morpholino-9H-pyrido[2,3-b]indol-3-yl)-1-phenylprop-2-en-1-one and its derivatives (5a-f) were synthesized by condensation reaction from the final intermediate, 2-morpholino-9H-pyrido[2,3-b]indol-3-carbaldehyde (4). The synthesis of the title compounds commenced from commercially available 21H-indol-2-amine (1) and by involving N-(1H-indol-2-yl)-acetamide (2) and 2-chloro-9H-pyrido[2,3-b]indole-3-carbaldehyde (3) as reactive intermediates. The chemical structure of synthesized compounds was characterized by IR, 1H NMR, mass spectral data and elemental analysis. The final compounds were used to screen for their antibacterial activity against various strains of bacteria.

Design, synthesis, and antiproliferative activity of new indole/1,2,4-triazole/chalcone hybrids as EGFR and/or c-MET inhibitors.

A novel group of indolyl-1,2,4-triazole-chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds 9a and 9e exhibited significant cancer inhibition with GI50 ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50-2.78 and 0.25-2.81 at the GI50 level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c-MET (mesenchymal-epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c-MET. Compound 9b showed the highest c-MET inhibition (IC50 = 4.70 nM) compared to foretinib (IC50 = 2.5 nM). Compound 9d showed equipotent activity compared with erlotinib against EGFR (IC50 = 0.052 µM) and displayed significant c-MET inhibition with an IC50 value of 4.90 nM.

Semisynthesis of novel chalcone hybrid compounds linked by 1,2,3-triazole and evaluation of their cytotoxic effects

A series of novel 1,2,3-triazole-chalcone hybrid compounds were designed and synthesized from thymol. The structural identity of the synthesized products 5a-h was unequivocally confirmed by spectroscopic techniques, including 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry (HRMS), and SC-XRD for 5b. The in vitro anticancer activity of the synthesized compounds was evaluated against a panel of four human cancer cell lines: fibrosarcoma (HT-1080), lung adenocarcinoma (A-549), and breast adenocarcinoma (MCF-7 and MDA-MB-231). Notably, most of the 1,2,3-triazole-chalcone hybrids (5a-h) displayed promising cell growth inhibition with IC50 values ranging from 4.61 to 50 μM. Furthermore, compounds 5a and 5b, bearing a 1-phenyl-1,2,3-triazole moiety and a 1-cyano-1,2,3-triazole moiety, respectively, exhibited particularly significant antiproliferative activity against HT-1080 cells. These compounds displayed impressive IC50 values of approximately 4.61 μM and 9.08 μM, respectively.

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

Novel 2-[thio]acetamide linked quinazoline/1,2,4-triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers.

Novel triazoloquinazolines carrying the 2-[thio]acetamide entity (4 and 5a-d) and triazoloquinazoline/chalcone hybrids incorporating the 2-[thio]acetamide linker (8a-b and 9a-f) were developed as anticancer candidates. NCI screening of the synthesized compounds at 10 μM concentration displayed growth inhibition not only up to 99.74% as observed for 9a but also a lethal effect could be achieved as stated for compounds 9c (RPMI-8226 and HCT-116) and 8b, 9a, and 9e on the HCT-116 cell line. The antiproliferative activity was determined for the chalcone series on three cell lines: RPMI-8226, HCT-116, and MCF-7. Compounds 8b, 9a, 9b, and 9f were the most active ones. To understand the mechanistic study, the inhibitory effect on the epidermal growth factor receptor (EGFR) kinase was evaluated. The results stated that the activity of compound 8b (IC50 = 0.07 μM) was near that of the reference drug erlotinib (IC50 = 0.052 μM) whereas compound 9b (IC50 = 0.045 μM) was found to be more potent than erlotinib. Both compounds 8b and 9b were selected for cell cycle analysis and apoptotic assays. Moreover, molecular docking results of the selected chalcone hybrids showed high binding scores and good binding affinities especially for 8b and 9b, which were consistent with the biological activity (EGFR).

Synthesis of New Pyrimidine Derivatives From 3-Acetylcoumarin–Chalcone Hybrid and Evaluation Their Antimicrobial Activitغe their antimicrobial activity y

3-coumarin/chalcone B1/B2/B3 hybrids served as malleable antecedents for the development of novel bioactive pharmacophores. In this study, the matching coumarin-chalcones hybrid was obtained from 3-acetylcoumarin (comp A) via condensation with several aromatic aldehydes in ethanolic piperidine solution. To further modify these hybrids, we reacted them with thiourea in the presence of base in ethanol, yielding pyrimidine derivatives C1, C2, and C3. Their chemical characteristics and spectroscopic data were used to characterize the newly synthesized heterocyles. The antibacterial efficacy of all freshly produced compounds was tested. Compound (C3) was shown to have the highest antibacterial activity against both gram positive and gram negative bacteria, whereas compound (C2) displayed a moderate antibacterial activity and compound C1 had low activity. C1,C2,C3 were shown antifungal activity as compared to fluconazole that showed antifungal efficacy against C. ablicans.

Synthesis, Characterization, Thermal and Dielectric Properties of Amino Acid-Centered Coumarin and Chalcone Hybrid Structures Via Click Reaction

Bu çalışma, kalkon ve kumarin grupları içeren amino asit konjugatlarının dielektrik özellikleri ve termal kararlılıklarının karşılaştırmalı bir analizini içermektedir. Bu konjugatların elektriksel davranışını incelemek amacıyla dielektrik sabiti, dielektrik kaybı ve AC iletkenliği araştırılırken, termal kararlılıklarını incelemek için termogravimetrik analiz (TGA) kullanılmıştır. Konjugatlar, kalkon veya kumarin yapılarının amino asit omurgalarına klik kimyası ile dahil edilmesiyle sentezlenmiştir. Dielektrik sabiti ölçümleri, kumarin bazlı amino asit konjugatlarının, kumarin sisteminin genişletilmiş π-konjugasyonu ve polarize edilebilirliği nedeniyle kalkon bazlı konjugatlara kıyasla daha yüksek değerler sergilediğini ortaya koymuştur. Dielektrik kayıp analizi, her iki konjugat türünün de yük transfer süreçleri ve moleküler hareketlerle ilişkili kayıplar sergilediğini göstermiştir. TGA ile termal stabilite değerlendirmesi, kalkon içeren konjugatın daha yüksek bozunma sıcaklıkları ile iyi termal stabilite sergilediğini ortaya koymuştur. Yüksek sıcaklıklarda gözlenen ağırlık kaybı, organik bileşenlerin termal bozunmasını göstermiştir. Bu etkili sonuçlar, dielektrik sabiti, dielektrik kaybı ve AC iletkenliği dahil olmak üzere dielektrik özelliklerin yanı sıra kalkon veya kumarin içeren amino asit konjugatlarının termal kararlılığı hakkında değerli bilgiler sağlamaktadır. Bulgular, elektronik cihazlar ve fonksiyonel malzemelerdeki potansiyel uygulamalar için önemli olan elektriksel davranışlarının ve termal özelliklerinin anlaşılmasına katkıda bulunmaktadır..

Chalcones: Effective Agents for Fighting Cancer Across Multiple Cell Lines

AbstractThis review article explores the mushrooming research on chalcone hybrid molecules as promising anticancer agents. Chalcones, featuring a unique chemical structure, exhibit diverse biological activities, including potent anticancer properties. Various synthetic chalcones and their derivatives have demonstrated remarkable efficacy against different cancer cell lines, offering advantages such as reduced mutagenicity. The article summarizes recent advancements in chalcone hybrid research, highlighting their potential in cancer treatment and paving the way for novel, safer, and more effective chemotherapeutic agents.

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications.

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationshipsas well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

Synthesis, characterization, and anticancer activity of 4,6-dichloropyrimidine chalcone hybrids and their mechanistic interaction studies with HSA: In-silico and spectroscopic investigations

Synthesis, characterization, and anticancer activity of 4,6-dichloropyrimidine chalcone hybrids and their mechanistic interaction studies with HSA: In-silico and spectroscopic investigations

Coumarin Chalcone Hybrids: Molecular Hybridization Strategy for Drug Design

Naturally occurring and synthetically produced hybrid compounds are potential reservoir for development of novel drug regimen because of various benefits including effectiveness, minimal side effects, receptor interactions and pharmacokinetic features. Coumarin and chalcone are perfect building blocks for creating hybrid scaffolds that can be used as bioactive agents. These are essential classes of synthetic chemistry with wide range of pharmacological properties. Encouraged by potential therapeutic and medicinal significance of these hybrids, the scientists have reported dozens of coumarin chalcone hybrids with a broad range of biological properties like antioxidant, analgesic, antimicrobial, antiviral, anticancer, antianxiety, antimalarial, anti-inflammatory etc. It is intended to support to medicinal researchers in the efficient, fruitful development of coumarin chalcone hybrids to maximize their biological potential. In view of these findings, we present here some literature review, synthetic methods and pharmacological efficacy, molecular targets.

Identification of novel sulfathiazole-triazolo-chalcone hybrids as VEGFR-2/EGFR dual inhibitors with antiangiogenic activity and apoptotic induction.

Certain sulfathiazole-triazolo chalcone hybrids were identified as anticancer agents with dual vascular endothelial growth factor receptor-2 (VEGFR-2)/epidermal growth factor receptor (EGFR) kinase inhibitory effect. All of the compounds were evaluated for their cytotoxic activity against the MCF-7 and HepG-2 tumor cell lines. Compounds 11g, 11h, and 11j exhibited the most potent antiproliferative activity against both cancer cell lines, with good safety toward WI-38 normal cells. Thus, they were further assessed for VEGFR-2 inhibitory activity. They have suppressed VEGFR-2 enzyme at IC50 of 0.316, 0.076, and 0.189 µM, respectively in comparison to sorafenib (IC50 = 0.035 µM). EGFR enzyme inhibition was further screened for the most potent inhibitors, 11h and 11j, where they displayed enhanced potency with IC50 of 0.085 and 0.108 µM, respectively, compared to erlotinib (IC50 = 0.037 µM). Compounds 11h and 11j were additionally investigated for inhibition of comparable kinases, PDGFR-β and B-Raf, where results assessed adequate selectivity of both compounds toward the VEGFR-2 and EGFR kinases. Furthermore, the wound healing assay of compound 11h manifested a percent wound closure of 65.18% in MCF-7 cells compared to doxorubicin (58.51%) and untreated cells (97.77%), proving its antiangiogenic activity. The cell cycle assay of MCF-7 cells treated with 11h demonstrated cell cycle arrest at the S phase. Moreover, compound 11h induced apoptosis with a 44-fold increase compared to that induced in the control MCF-7 cells. Molecular docking results of compounds 11h and 11j established their efficacies, and in silico studies showed convenient safety profiles with drug-likeness properties.

Design, Synthesis, and Antiproliferative Activity of Quinazolin-4-One/Chalcone Hybrids via the EGFR Inhibition Pathway.

Quinazolinone scaffolds have drawn international attention due to their potent anticancer activity and therapeutic applications. Furthermore, Chalcone and Oxime are special chemical templates with a wide range of biological activities, including anti-cancer activity. As a result, the purpose of this research is to synthesize and develop a new series of 2-thioxo-3-substituted quinazolin-4-one/chalcone analogues and 2-thioxo-3-substituted quinazolin-4-one/oximes analogues in order to obtain a new cytotoxic agent that can target epidermal growth factor (EGFR) and/or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAFV600E) oncogene. All synthesised compounds were tested for anticancer activity against four human cancer cell lines. The new hybrids' potential anti-cancer mechanism was evaluated using EGFR and BRAF enzymatic tests. The most active molecules within the target enzyme's active site were studied using molecular docking. Apoptosis and cell cycle analysis were also investigated. The target compounds 7a-j (series I) are obtained in high yields by alkylation of 2-mercapto-3-ethyl-(3H)- quinazolin-4-one 3a with acylated chalcones 6a-j. Alkylation of compounds 3b-c with N-(4-acetylphenyl)-2- bromoacetamide 8, the corresponding ketones intermediates 9b-c was produced in high yields. Compounds 7a-j, 9b-c, and 10b-c were tested for their antiproliferative activity against four human cancer cell lines using the MTT assay and doxorubicin as a control drug. The EGFR and BRAF assay tests were used to assess the inhibitory potency against EGFR and BRAF. Compounds 7c, 7d, 7f and 10c exhibited high proliferative activity and inhibited EGFR, which could serve as a potential target for antiproliferative activity. The most active hybrid, 7c, primarily caused cell cycle arrest in G0/G1 phase and S phase as well as cell apoptosis. Finally, the most active hybrids were docked well to the EGFR active site. 2-thioxo-3-substituted quinazolin-4-one/chalcone derivatives have significant apoptotic and antiproliferative properties.

Synthesis, In Vitro and In Silico Biological Studies of 1, 2, 3-Triazole-Furan Chalcone Hybrids

In the present investigation, we focused our interest to develop 1, 2, 3-triazolefuran chalcone hybrids along with their biological profile. The synthesis of target molecules involves sequence of reactions, namely diazotization, nucleophilic substitution, cycloaddition and finally, solvent-free Claisen–Schmidt condensation reaction. The biological profile of the synthesized compounds was carried out using prediction of activity spectra for substances and results revealed that the synthesized compounds may act as mild antimicrobial agents.

Chalcone/1,3,4-Oxadiazole/Benzimidazole hybrids as novel anti-proliferative agents inducing apoptosis and inhibiting EGFR & BRAFV600E

IntroductionOne of the most robust global challenges and difficulties in the 21st century is cancer. Treating cancer is a goal which continues to motivate researchers to innovate in design and development of new treatments to help battle the disease.ObjectivesOur objective was developing new antiapoptotic hybrids based on biologically active heterocyclic motifs "benzimidazole?oxadiazole-chalcone hybrids'' that had shown promising ability to inhibit EGFR and induce apoptosis. We expected these scaffolds to display anticancer activity via inhibition of BRAF, EGFR, and Bcl-2 and induction of apoptosis through activation of caspases.MethodsThe new hybrids 7a-x were evaluated for their anti-proliferative, EGFR & BRAFV600E inhibitory, and apoptosis induction activities were detected. Docking study & dynamic stimulation into EGFR and BRAFV600E were studied.ResultsAll hybrids exhibited remarkable cell growth inhibition on the four tested cell lines with IC50 ranging from 0.95 μM to 12.50 μM. which was comparable to Doxorubicin. Compounds 7k-m had the most potent EGFR inhibitory activity. While, compounds 7e, 7g, 7k and 7l showed good inhibitory activities against BRAFV600E. Furthermore, Compounds 7k, 7l, and 7m increased Caspases 3,8 & 9, Cytochrome C and Bax levels and decreased Bcl-2 protein levels. Compounds 7k-m received the best binding scores and showed binding modes that were almost identical to each other and comparable with that of the co-crystalized Erlotinib in EGFR and BRAF active sites.ConclusionCompounds 7k-m could be used as potential apoptotic anti-proliferative agents upon further optimization.

Synthesis, anticancer activity, molecular docking and molecular dynamics studies of some pyrazole–chalcone hybrids

Four new hybrid compounds (H1–H4) bearing pyrazole (S1 and S2) and chalcone (P1 and P2) fragments were synthesized and characterized. Compounds were assayed for their ability to inhibit the proliferation of human lung (A549) and colon (Caco-2) cancer cell lines. Besides, toxicity against normal cells was determined using the human umbilical vein endothelial cells (HUVEC). In silico molecular docking, molecular dynamics (MD) simulation and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were carried out to predict the binding modes, protein stability, drug-likeness and toxicity of the reported compounds. The in vitro anticancer activity of the tested compounds revealed dose-dependent cell-specific cytotoxicity. In silico studies revealed that the compounds have a good binding affinity, possess appropriate drug-likeness properties and have low toxicity profiles. Communicated by Ramaswamy H. Sarma

Design, Synthesis and Anticancer Activity of New Benzofuran‐Chalcone Hybrids and Their Water Soluble Sodium Salts

AbstractIn this study, firstly, 1‐(7‐ethoxy‐1‐benzofuran‐2‐yl) ethanone and 1,1’‐(7‐ethoxy‐1‐benzofuran‐2,4‐diyl)diethanone were synthesized for the starting reagent purposes. The synthesized benzofuran‐chalcone salts were soluble in water at room temperature. Structural analysis of the synthesized compounds was characterized by elemental analysis, FT‐IR and NMR spectroscopy techniques. The anticancer activities of the compounds were determined by SRB viability assay in human lung cancer (A549, H1299) and breast cancer (MCF‐7, MDA‐MB‐231) cell lines. Findings for apoptosis were determined by flow cytometry analysis and the PARP‐ELISA method. The results of the in vitro SRB analysis of the compounds showed that some of the chalcone hybrids were very effective on both types of cancer in a dose and time‐dependent manner. Treatment of all cancer cell types with these hybrids resulted in a significant increase in the percentage of early and mainly late apoptotic cells, demonstrating their apoptosis‐inducing effects via the Caspase 3/7 Activity.

Design, synthesis, cytotoxic activities, and molecular docking of chalcone hybrids bearing 8-hydroxyquinoline moiety with dual tubulin/EGFR kinase inhibition

The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a–mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine. The enzymatic assay revealed that3e,3d, and3ihad goodtubulin polymerization inhibition (IC50 = 5.3, 8.6, and 8.05 µM, respectively) compared to the reference Combretastatin A4 (IC50 = 2.15 µM). Moreover,3e,3l, and3fexhibited EGFR inhibition (IC50 = 0.097, 0.154, and 0.334 µM, respectively) compared to Erlotinib (IC50 = 0.056 µM). Compounds3eand3fwere investigated for their effects on the cell cycle, apoptosis induction, andwnt1/β-cateningene suppression. The apoptosis markers Bax, Bcl2, Casp3, Casp9, PARP1, and β-actin were detected by Western blot. In-silico molecular docking, physicochemical, and pharmacokinetic studies were implemented for the validation of dual mechanisms and other bioavailability standards. Hence, Compounds3eand3fare promising antiproliferative leads with tubulin polymerization and EGFR kinase inhibition.

Novel Erlotinib–Chalcone Hybrids Diminish Resistance in Head and Neck Cancer by Inducing Multiple Cell Death Mechanisms

In a search for novel therapeutic options for head and neck squamous cell carcinomas (HNSCCs) generally treated with limited therapeutic success, we synthesized a series of novel erlotinib-chalcone molecular hybrids with 1,2,3-triazole and alkyne linkers and evaluated them for their anticancer activity on Fadu, Detroit 562 and SCC-25 HNSCC cell lines. Time- and dose-dependent cell viability measurements disclosed a significantly increased efficiency of the hybrids compared to the 1:1 combination of erlotinib and a reference chalcone. The clonogenic assay demonstrated that hybrids eradicate HNSCC cells in low micromolar concentrations. Experiments focusing on potential molecular targets indicate that the hybrids trigger the anticancer effect by a complementary mechanism of action that is independent of the canonical targets of their molecular fragments. Confocal microscopic imaging and real-time apoptosis/necrosis detection assay pointed to slightly different cell death mechanisms induced by the most prominent triazole- and alkyne-tethered hybrids (6a and 13, respectively). While 6a featured the lowest IC50 values on each of the three HNSCC cell lines, in Detroit 562 cells, this hybrid induced necrosis more markedly compared to 13. The therapeutic potential indicated by the observed anticancer efficacy of our selected hybrid molecules validates the concept of development and justifies further investigation to reveal the underlying mechanism of action.

A three-step pathway from (2-aminophenyl)chalcones to novel styrylquinoline-chalcone hybrids: synthesis and spectroscopic and structural characterization of three examples.

Three new styrylquinoline-chalcone hybrids have been synthesized using a three-step pathway starting with Friedländer cyclocondensation between (2-aminophenyl)chalcones and acetone to give 2-methyl-4-styrylquinolines, followed by selective oxidation to the 2-formyl analogues, and finally Claisen-Schmidt condensation between the formyl intermediates and 1-acetylnaphthalene. All intermediates and the final products have been fully characterized by IR and 1H/13C NMR spectroscopy, and by high-resolution mass spectrometry, and the three products have been characterized by single-crystal X-ray diffraction. The molecular conformations of (E)-3-{4-[(E)-2-phenylethenyl]quinolin-2-yl}-1-(naphthalen-1-yl)prop-2-en-1-one, C30H21NO, (IVa), and (E)-3-{4-[(E)-2-(4-fluorophenyl)ethenyl]quinolin-2-yl}-1-(naphthalen-1-yl)prop-2-en-1-one, C30H20FNO, (IVb), are very similar. In each compound, the molecules are linked into a three-dimensional array by hydrogen bonds, of the C-H...O and C-H...N types in (IVa), and of the C-H...O and C-H...π types in (IVb), and by two independent π-π stacking interactions. By contrast, the conformation of the chalcone unit in (E)-3-{4-[(E)-2-(2-chlorophenyl)ethenyl]quinolin-2-yl}-1-(naphthalen-1-yl)prop-2-en-1-one, C30H20ClNO, (IVc), differs from those in (IVa) and (IVb). There are only weak hydrogen bonds in the structure of (IVc), but a single rather weak π-π stacking interaction links the molecules into chains. Comparisons are made with some related structures.