Lawesson’s reagent is used with β-enaminone to synthesize the compound (Z)-1,3-diphenyl-3-(phenylamino) prop-2-ene-1-thione. The 6–311 + + G(d,p) basis set is employed to evaluate the stability of the molecule’s probable tautomers via DFT with the functionals ωB97XD, M062X, B3LYP, and CAM-B3LYP. The ρBCP value for the hydrogen bond in the gas phase ranges from 0.035962 to 0.038105 e/a03. The intramolecular hydrogen bonding is relatively weak, as evidenced by atoms in molecules (AIM) computations conducted across several media and theoretical models. We examine the nonlinear optical (NLO) properties of enaminothione after illuminating with two continuous wave (CW) laser beams. We employ diffraction patterns (DPs) and the closed aperture (CA) Z-scan techniques to determine the nonlinear refractive index (NLRI) of enaminothione. The NLRI is equal 4.996 × 10–7 cm2/W at the wavelength 473 nm. The application of 473 nm and 532 nm laser beams on enaminothione has demonstrated its ability to transition between all-optical switching (AOS).

In the present work, a microwave-promoted one-pot three components reaction catalyzed by 1, 4-diazabicyclo[2.2.2]octane (DABCO) was developed for the scalable synthesis of a new series of tetra-substituted pyrrole derivatives 4a-j. The targeting pyrroles 4a-j with a diverse functionality on the central pyrrole ring were examined for their antiproliferative activity using MTT assay on three esophageal squamous carcinoma cells (EC109, SKGT-4, and KYSE-450) in addition to two healthy cells (HET-1A and NE-1). Among the tested pyrrole derivatives, compounds 4e, 4g, 4h, 4i, and 4j exhibited significant antiproliferative activity compared to cisplatin as a standard drug. In the cellular apoptotic test, the most potent derivatives are found to have a significant behavior for inducing apoptotic cell death in cancerous cells. After the kinetic mechanism model of enzymatic inhibition was determined, the pyrrole derivatives were conducted to molecular docking and molecular dynamics (MD) computations to investigate their potential interactions with the targeting proteins (code PDB ID: 5HZN, 6DUK, and 2LEO). The molecular docking and dynamics scores revealed that the most potent derivatives constituted good protein-ligand systems through hydrogen bonding and hydrophobic interactions. The experimental and theoretical findings revealed that the most potent pyrroles might occupy a significant position in esophageal cancer treatment.

A new series of bis-(aryl-based chalcone) derivatives 9-15 derived from 4,4 '-(ethane-1,2-diylbis(oxy))-bisbenzaldehyde (8) were synthesized, via Claisen-Schmidt condensation, under microwave irradiation (MWI). The newly synthesized bis-chalcones were characterized on the basis of their chemical properties and spectroscopic data. All the synthesized analogues were evaluated for their in vitro antiproliferative activity against breast adenocarcinoma of the CAL51 cell line by MTT assay. Compounds 9 and 10 exhibited the highest cytotoxic activity, with inhibitions of 78.2 % and 74.4 %, respectively, at a concentration of 10 mu M. Furthermore, compounds 9-15 were evaluated for their antibacterial activity. The docking of compounds 9 and 10 with the protein kinase TTK (PDB: 7CHN, 7CIL) related to the triple negative breast cancer (TNBC) was studied to predict their possible binding modes with the kinase. The docking results were agreed with the protein kinase TKK inhibitory studies. Furthermore, the computational analysis was carried out to investigate the molecular structures of the new molecules. These results suggest that analogues 9 and 10 could be promising lead compounds for the continued development of novel antiproliferative agents. The molecular dynamics simulation with computational studies has been performed.

This study examines the structural properties of intramolecularly hydrogen-bonded vinylogous thiocarboxamides through NMR spectroscopy, isotope effects on chemical shifts, atoms-in-molecules (AIM), and density functional theory (DFT) calculations. The functionals omega B97XD, M062X, CAM-B3LYP, and B3LYP using the (6-311++G) (d, p) basis set were used for the DFT calculations. This study characterized three tautomers of vinylogous thiocarboxamide derivatives, with the enaminothione tautomer having the highest stability. The AIM analysis demonstrated that the hydrogen bonds in these systems exhibit moderate strength. This study also revealed correlations between the strengths of hydrogen bonds and different geometric parameters, providing a novel understanding of the physicochemical features of these systems. The combination of computational models and experimental data yields a thorough comprehension of the intramolecular hydrogen bonding in vinylogous thiocarboxamide derivatives, hence offering insights for future chemical synthesis and functionalization approaches.

A simple and efficient protocol was developed for the visible light-induced cyclization of a hydrazone derivative to afford a new 3-acetyl-2,3-dihydro-1,3,4-oxadiazole derivative 6(C17H14N2O4). The protocol proceeded smoothly, with high yield of the target product at room temperature in the absence of any photocatalysts under an air atmosphere. After structural optimization of the target derivative 6, its efficiency was elucidated using density functional theory (DFT)-assisted calculations with two functional hybrids, B3LYP/cc-pVTZ and M062X/cc-pVTZ, to verify the important electronic descriptors including highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) as frontier orbitals, ΔEgap (E HOMO − E LUMO), polarizability, and hyperpolarizability. The nonlinear optical (NLO) properties of the target derivative 6 were studied using the diffraction patterns (DPs) and Z-scan methods. DPs were formed due to the interference of beams emanating from enormous points on the laser beam wave front and on the semitransparent screen situated in the far field related to the sample cell. In the closed aperture Z-scan case, we observed the phenomenon of self-defocusing (SDF) of the laser beam transmitted from the target sample. The origin of the nonlinearity shown by the sample was thermal due to the use of a continuous-wave (CW) laser beam. At the maximum power input, the number of the formed rings and the Z-scan were utilized to obtain two values of the nonlinear refractive index (NLRI), n2, i.e., 5.9949 × 10−7 and 0.344 × 10−7 cm2/W, respectively. By applying 473 nm as the controlling beam and 532 and 635 nm as the controlled beams, both static and dynamic all-optical switching (AOS) were studied.

A series of 4‐nitroimidazole‐piperazine conjugated 3,5‐disubstituted isoxazole analogs 9a‐o were synthesized using nitrile oxide/alkyne cycloadditions (NOAC) with good yields. The antiproliferative activities of these compounds were evaluated against breast cancer cell lines MCF‐7 and MDA‐MB‐231, as well as prostate cancer cell lines PC‐3 and DU‐145. Notably, compounds 9a , 9j , 9k , and 9o exhibited significant antiproliferative effects against MCF‐7 cells, with IC 50 values ranging from 0.052 to 0.012 µM, while no activity was observed against the MDA‐MB‐231 cell line. Additionally, compounds 9a , 9d , 9g , 9j , and 9k showed significant cytotoxicity against PC‐3 cells, with IC 50 values between 0.156 and 0.041 µM. Compounds 9a , 9j , 9k , and 9o also demonstrated antiproliferative activity against DU‐145 cells, with IC 50 values ranging from 1.18 to 0.356 µM. Molecular docking studies revealed that compound 9a exhibited strong binding interactions with human protein receptors ER, PR, and HER2, while compound 9j showed significant binding affinity with the androgen receptor CYPP450 17A1.

A new series of cis-β-lactam derivatives was synthesized from the anti-inflammatory drugs diclofenac and sulindac via a Staudinger [2 + 2] cycloaddition of ketenes with various imines, and the exclusively formed cycloadducts were fully characterized by spectroscopic methods. All synthesized compounds were screened for antiproliferative activity against MCF-7 breast cancer cells. Among them, compound 16 proved most potent (IC50 = 21.74 µM; SI = 36.1) and was further evaluated against A375 melanoma cells (IC50 = 168.0 µM; SI = 1.2). Furthermore, the total antioxidant capacity of compounds 12, 13, and 15-17 was assessed. Molecular docking studies of the mitotic kinase TTK showed strong binding for all compounds, with compounds 16 and 17 displaying especially strong interactions in the TTK-binding pocket, supporting experimental kinase inhibition findings. Computational analyses, including DFT calculations, revealed that compounds 16 and 17 possess favorable electronic properties, with lower HOMO-LUMO gaps suggesting enhanced reactivity. ADMET predictions revealed favorable pharmacokinetic properties for all compounds, with compounds 16 and 17 exhibiting good membrane permeability, minimal toxicity aside from immunotoxicity, and adequate bioavailability. In addition, molecular dynamics simulations confirmed the structural stability and sustained binding of the 16-TTK and 17-TTK complexes under physiological conditions.

A series of 2-(2-arylidenehydrazinyl)-4,6-bis(substituted-phenoxy)-1,3,5-triazines (compounds 3a-o to 7a-o) was synthesized and evaluated for DNA-binding affinity using calf thymus DNA. Based on their DNA interaction profiles, the top three compounds from each series were selected for in vitro anticancer screening against eight human cancer cell lines, encompassing both solid tumors (glioblastoma, pancreatic adenocarcinoma, colorectal carcinoma, and lung carcinoma) and hematological malignancies (acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, and non-Hodgkin lymphoma). Among the tested compounds, 5i and 7b demonstrated the highest anticancer potency against pancreatic adenocarcinoma (Capan-1), with IC50 values of 2.4 and 1.9 µM, respectively. Notably, compound 5i also exhibited strong cytotoxicity against colorectal carcinoma (HCT-116), with an IC50 of 2.2 µM. Additional analogues namely 3i, 3l, 6g, 6l, and 7m displayed IC50 values ranging from 7.4 to 42.2 µM across the panel of cancer cell lines, highlighting the superior activity of 5i and 7b as promising antiproliferative agents. Molecular docking studies revealed that compound 7b formed strong interactions with the prenyl-binding protein PDEδ, and subsequent molecular dynamics simulations confirmed the stability of the 7b-PDEδ complex, supporting its potential as a targeted anticancer agent.

A series of 1-(4-chlorobenzhydryl) piperazine derivatives 3-10 were synthesized and characterized both spectroscopically and structurally to investigate their antiproliferative activity associated with the piperazine framework. The compounds were screened against seven human cell lines. Analogously, compounds 14-16 were prepared from treatment of 2 with 4-((2-aminothiazol-4-yl)amino)phenol (11), 4-((2-aminothiazol-4-yl)phenol (12) or 2-amino-5-methoxybenzothiazole (13) in the presence of K2CO3 and KI. Compounds 7 and 10 displayed the highest potency, where 7 exhibited an IC50 value of 6.85 mu M against the Z-138-non Hodgkin lymphoma cancer cell line, and 10 showed IC50 of 7.40 mu M against the DND-41 acute lymphoblastic leukemia cancer cell line. However, all compounds demonstrated IC50 values ranging from 22.0 to > 100 mu M against other tested cancer cell lines. These findings suggest that compounds 7 and 10 hold promise as potential lead compounds for the development of novel antiproliferative agents. Furthermore, compounds 3-10, and 14-16 were evaluated for their antioxidant activity. The study encompassed the molecular docking analysis of compound 7 alongside specific amino acids present in Z-138-non-Hodgkin lymphoma (phosphoinositide 3-kinase, protein PI3k delta, PDB: 4XE0), as well as the docking assessment of compound 10 with the amino acids present in DND-41-acute lymphoblastic leukemia (receptor tyrosine phosphatase (PTPRC/CD45, PDB: 1YGR). The molecular dynamics simulation as well as the DFT have been performed.

A new series of 4-nitroimidazole bearing substituted aryl piperazines 7-16, tetrazole 17 and 1,3,4-thiadiazole 18 derivatives was designed and synthesized. All derivatives were screened for their anticancer activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI-H460, DND-41, HL-60, K562 and Z138). Compound 17 proved the most potent compound of the series inhibiting proliferation of most of the selected human cancer cell lines with IC50 values in the low micromolar range. In addition, compound 11 exhibited IC50 values ranging 8.60 to 64.0 μM against a selection of cancer cell lines, whereas compound 18 showed IC50 values varying between 8.25 and 43.55 μM against all the selected cancer cell lines, whereas. These findings suggest that derivative 17 can potentially be a new lead compound for further development of novel antiproliferative agents. Additionally, compounds 17-18 were assessed for their antibacterial and antituberculosis activity, where derivatives 17 and 18 were the most potent compounds of the series against both Staphylococcus aureus strain Wichita and a methicillin resistant strain of Staphylococcus aureus (MRSA), as well as against M. tuberculosis strain mc26230. The antiviral activity of compounds 7-18 was also evaluated but no activity was found against the selected viruses. The docking studies were conducted to predict the interaction of derivative 17 with putative protein targets in acute myeloid leukemia, specifically Fms-like tyrosine kinase-3 (FLT3). The results showed a docking score of -8.132 kcal/mol-1, indicating a strong binding affinity. Additionally, it was observed that derivative 17 exhibited favorable hydrophobic interactions with the active site of the tyrosine kinase-3. Furthermore, the analysis of the 200 ns molecular dynamics simulation results based on the best-docked complexes 17 and 18 with tyrosine kinase-3 receptor demonstrates stable interactions, and the complexes undergo the same conformational fluctuations. The average of the calculated binding free energy of complex 17 and 18 are -184.6 kJ/mol and -160.2 kJ/mol, respectively, and the result demonstrated that complex 17 promoted higher stability than complex 18 to the tyrosine kinase-3.

On the basis of remarkable anticancer profile of s-triazine nucleus, a new series of 2-methoxy-4-(3-morpholino-5-(arylamino)phenoxy)benzaldehyde derivatives 11 a-u was prepared and evaluated for in vitro antiproliferative activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI-H460, DND-41, HL-60, K562 and Z138). Compounds 11 o, 11 r and 11 s were the most potent anticancer agents on pancreatic adenocarcinoma (Capan-1) cell line with IC50 value of 1.4, 5.1 and 5.3 μM, respectively, while compounds 11 f, 11 g, 11 k, 11 l and 11 n displayed selective activity against the pancreatic adenocarcinoma (Capan-1) cell line with IC50 values of 7.3-11.5 μM. These results indicate that derivative 11 o may serve as a promising lead compound for the ongoing development of novel antiproliferative agents. The docking studies were conducted to predict the interactions of derivative 11 o with putative protein targets in pancreatic adenocarcinoma (Capan-1) cell line, specifically the prenyl-binding protein PDEδ. Furthermore, the analysis of the molecular dynamics simulation results demonstrated that complex 11 o promoted a higher stability to the prenyl-binding protein PDEδ.

The compound, (Z)-3-((4-(diethylamino)phenyl)amino)-1,3-diphenylprop-2-en-1-one, is synthesized by the reaction of dibenzoylmethane and 4-N,N-diethylaniline. The relative stabilities of the possible tautomers of the molecule are studied via the DFT B3LYP-D3BJ, CAM-B3LYP, M062X, and omega B97XD functionals in conjunction with the 6-311++G(d,p) basis set. The results showed that the enaminone tautomer with the intramolecularly hydrogen bonded chelated ring is the most stable. This is further confirmed by the Car-Parrinello MD calculations in the gas phase as well as the NCI analysis. The electronic spectrum is calculated by the TD DFT B3LYP/c-pVDZ level in ethanol, and the hole-electron analysis is carried out for the interpretation of the bands, which revealed that the longest one at 430 nm is of charge transfer origin while the others are of local transition origin. Atoms-in-molecules calculations in several media and levels of theory predicted that the rho BCP at the hydrogen bond in the gas phase to be 0.03791-0.04255 e/a(0)(3) which is a characteristic of a medium strong hydrogen bond. Researchers investigated the enaminone's nonlinear optical (NLO) characteristics when it was exposed to a low power (<1 Watt), single fundamental transverse mode laser beam at 473 nm. By using diffraction patterns (DPs) and Z-scan methods, we calculated the nonlinear refractive index (NLRI) of the enaminone up to 4.597 x 10(-11) m(2) W-1 using DPs. The resulting DPs are numerically investigated using the Fraunhofer (F.) approximation and the Fresnel-Kirchhoff (F.K.) diffraction integral, showing excellent agreement with experimental findings. We successfully explored all-optical switching (AOS) in enaminone using two laser beams.

Herein, a novel series of 1,5-disubstituted-1,2,3-triazolines containing 1-(4-chlorobenzhydryl) piperazine moiety (8-18) were synthesised and evaluated for their anticancer activity across eight human tumor cell lines. Remarkably, compound 11 substituted with 3-acetylphenyl group was the most potent anticancer agent against three selected human cancer cell lines (HL-60, Z138, and DND-41) with IC50 values of 16.80, 18.50, and 19.20 mu M, respectively. In contrast, analogue 10 demonstrated activity against HL-60, Z138, and DND-41 cell lines, with IC50 values of 19.90, 18.00, and 18.50 mu M, respectively. Moreover, derivative 13 substituted with 4-bromophenyl moiety displayed activity with IC50=19.90 mu M against the DND-41 cell line. However, all analogues showed IC50 values ranging from 22.95 to 58.45 mu M when tested against other investigated cancer cell lines. These findings suggest that derivative 11 holds promise as a potential candidate for synthesizing novel anticancer agents. Furthermore, compounds 8-18 were screened for their antioxidant activity. Molecular docking studies of compound 11 on crystal structures of two proteins, CDK2/cyclin A2 (PDB: 7B7S) and kinase Akt1 PKB alpha (PDB: 4GV1) have been studied.

Abstract A new series of derivatives (compounds 8–20) of the breast antihormonal drug letrozole tagged with additional aryl groups were synthesized starting from the letrozole analog 7 via Suzuki cross-coupling reaction. Treatment of the ketone 9 with various aldehydes in base afforded the chalcone analogs 21–27. The structural assignments were done by IR, 1H, 13C and 2D NMR spectra. Compounds 13, 21–23, 25 and 26 have been selected for their anticancer activity against MCF-7 and WRL-68 cell lines. Compounds 13 and 22 were found to be the most potent anticancer agents with IC50 values of 34.75 and 58.79 (μg mL−1) (SI = 3.3 and 2.6, respectively). Molecular docking study of compounds 13 and 22 revealed hydrogen bond with the amino acids Arg115, Met374 and Met364 residues of the receptor 3EQM, respectively. Therefore, compounds 13 and 22 can be considered as promising anticancer agents due to their potent cytotoxic activity.

Abstract To investigate the antiproliferative activity associated with the piperazine framework, a series of benzhydryl piperazine derivatives 8–18 were synthesized and characterized both spectroscopically and structurally. The antiproliferative activity of these compounds against eight human tumor cell lines was assessed. Among the tested compounds, compound 11 exhibited the highest potency, effectively inhibiting the proliferation of three selected human cancer cell lines, HL-60, Z138, and DND-41 with IC50 values of 16.80, 18.50 and 19.20 µM, respectively. Compound 10 displayed IC50 values of 19.90, 18.00 and 18.50 µM against the cell lines HL-60, Z138 and DND-41, whereas compound 13 showed IC50 value of 19.90 µM against cell line DND-41. However, all compounds exhibited IC50 values ranging from 22.95 and 58.45 µM against other tested cancer cell lines. These finding suggest that derivative 11 would be a promising potential lead compound for the development of novel antiproliferative agents. Further compounds 8–18 were evaluated for their antioxidant activity. Additionally, predictive docking studies were performed on the three-dimensional structures of acute myeloid leukemia (CDK2/cyclin A2, PDB: 7B7S, and protein kinase Akt1 PKB alpha, PDB: 4GV1).

In this work OR1(E1,6E) -1,7-bis (4-propyloxy phenyl) hepta-1,6-diene-3,5 dione compound is synthesized. The compound has been characterized via computational technique by studying the molecule’s electronic structures through calculating its HOMO and LUMO energies, and its band gap energy (E HOMO -E LUMO ). The nonlinear refractive index (NLRI) of the solution of OR1 compound in DMF solvent is determined using diffraction patterns (DPs) which resulted when a continuous wave laser beam of wavelength 473 nm traversed the compound solution in a glass cell of 1 mm thickness. By counting the number of rings under maximum beam input power, the NLRI of value 10 − 6 cm 2 /W resulted. The NLRI is calculated once more via the Z-scan technique and a value of 0.25 × 10 − 7 cm 2 /W is obtained. The vertical convection current in the OR1 compound solution appears to be responsible for the asymmetries noticed in the DPs. The temporal variation of each DP is noticed together with the evolution of DPs against beam input power. DPs are numerically simulated based on the Fresnel-Kirchhoff integral with good accord compared to the experimental findings. Dynamic and static all-optical switching in the OR1 compound using two laser beams (473 and 532 nm ) is tested successfully.

In this study, we conducted the synthesis and diagnosis of compound denoted as 1A3, specifically, (2E,4E,9E,11E)-7-chloro-2,12-diphenyltrideca-2,4,9,11-tetraene-6,8-dione. The photoluminescent and UV-vis spectral properties of this compound are investigated. The compound is dissolved in both chloroform and DMF for analysis purposes. Compound 1A3's nonlinear optical (NLO) characteristics when dissolved in DMF, are extensively studied through a series of experiments including diffraction patterns (DPs) and Z-scan. The optical limiting (OL) property of the 1A3 compound is tested and a threshold value of 12.4 mW at the wavelength 473 nm is obtained. Additionally, we explored its potential for all-optical switching utilizing two low-power visible laser beams. Notably, we achieved a significant nonlinear refractive index (NLRI) reaching up to 5.921 x 10 -11 m 2 /W. To analyze the obtained diffraction patterns, we employed the Fresnel-Kirchhoff integral equation and conducted meticulous simulations. The numerical outcomes showed satisfactory agreement with the experimental observations.

Cancer is a leading cause of death worldwide. Osteoporosis is a bone condition that causes the bones to become porous and lose density. Discovering, searching, and develop for a drug against cancer and at the same time preventing osteoporosis is very important. Chalcone and epoxy have an interest as potential drug candidates due to their easy synthesis. The present study target compounds were screened for potential anti-cancer against different cell lines (HepG2, MDA-MB-231, A375, A549, MCF-7, and HCT116) and anti-osteoporosis against cell line (MC3T3-E1). A new series of compounds evaluation by MTT assay to determine the IC50, and study apoptosis and docking study. The most potent activities were the effects of the compounds CH2, CH3, and CH4 on the MDA-MB-231 cells and those of the compounds CH7 and CH9 on the HepG2. The CH7 compound proved non-cytotoxicbut was antiproliferative and caused cell cycle arrest at the G0/G1 and G2/M phases. Also, the CH7, CH9, and E1 compounds displayed excellent anti-osteoporosis activity. The docking analysis showed good binding energy. The compounds CH2, CH3, and CH4 exhibited activity towards MDA-MB-231 cells and CH7 against HepG2, with induced apoptosis and cell cycle arrest, others compounds showed no significant cytotoxic activity. While compounds CH7, CH8, CH9, and E1 showed good toxicity against MC3T3-E1. The molecular docking study revealed that there was evidence of good interactions and the most stable complex for inhibition.

A new series of the anti-inflammatory drug ketoprofen derivatives bearing aryl chalcone-amide congeners were synthesized. The structures of the synthesized compounds were identified by the 1H NMR, 13C NMR, and EIMS spectroscopic methods. The inhibitory activity of the synthesized compounds on cholinesterase enzymes was investigated. Biological results revealed that five compounds displayed moderate activities against acetylcholinesterase (AChE) with IC50 values below 10 μM. Among the tested compounds, (BTPhP) was found to be the most potent against AChE (IC50 0.98 ± 0.02 μM), while the chalcone-amide analogues (MeOPh), (HydPh), (FPh), and (ChPh) exhibited moderate activities with IC50 values ranged between 5.19–9.61 μM. Molecular docking study showed that compound (BTPhP) could combine with the active site of acetylcholinesterase by the π–π between the ketoprofen phenyl groups is embedded in a cavity surrounded by two aromatic residues of Tyr334 and Trp279. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, compound (BTPhP) emerged as a promising lead for the development of new acetylcholinesterase inhibitor agent. The preliminary quantum structure-activity relationship (QSAR) among the newly synthesized congeners was obtained by Genetic Function Approximation (GFA).

Abstract The development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.