Thienopyrimidines represent an important class of nitrogen- and sulfur-containing heterocycles with broad pharmacological relevance. In this work, a new series of thienopyrimidine derivatives was efficiently synthesized through a multistep route involving cyclization, Mannich annulation, Schiff-base condensation, dipyrimidinone ring formation, and acylation, affording structurally diverse fused frameworks. The synthesized compounds were fully characterized using IR, NMR, and mass spectrometry. Their antimicrobial activity was evaluated against representative Gram-positive, Gram-negative strains and fungal strains revealing clear structure-activity relationships. Notably, the Mannich derivative 11 exhibited the highest potency toward Bacillus subtilis, while the fused dipyrimidinone compound 13 demonstrated broadened activity, including inhibition of Escherichia coli. Density functional theory (DFT) calculations provided insight into the electronic structure, intramolecular interactions, HOMO-LUMO distributions, electrostatic potential surfaces, and noncovalent interaction patterns responsible for the observed reactivity and binding behavior. Molecular docking studies against B. subtilis and E. coli DNA gyrase B revealed strong and diverse protein-ligand interactions, consistent with the biological findings, and highlighted compound 13 as the most promising candidate due to its favorable Vina score and extensive hydrogen-bonding and hydrophobic contacts. Collectively, the combined synthetic, biological, and computational analyses underscore the potential of thienopyrimidine scaffolds as valuable agents for developing new antimicrobial agents.

Cancer remains a leading cause of mortality worldwide, necessitating the continuous development of more effective and selective therapeutic agents. Among heterocyclic scaffolds, 1,3,4-thiadiazole derivatives have attracted considerable attention due to their diverse pharmacological properties and favorable physicochemical characteristics. In this study, a novel thiadiazole-based compound namely 2-((5-acetamido-1,3,4-thiadiazol-2-yl)thio)-N-(naphthalen-2-yl)acetamide, was successfully synthesized in excellent yield (99%) and high thermal stability and was fully structurally characterized using FT-IR, NMR, and mass spectrometry. The anticancer potential of the synthesized compound was evaluated in vitro against three human cancer cell lines, namely breast adenocarcinoma (MCF-7), colorectal carcinoma (HCT-116), and hepatocellular carcinoma (HepG-2), using the MTT assay. The compound exhibited pronounced cytotoxic activity against MCF-7 and HCT-116 cell lines, with IC50 values of 1.07 ± 0.03 µM and 2.09 ± 0.55 µM, respectively, demonstrating superior potency compared to the reference drug doxorubicin. In contrast, no significant activity was observed against HepG-2 cells, indicating a degree of selectivity. These findings highlight the potential of the 1,3,4-thiadiazole scaffold as a promising platform for the development of novel anticancer agents with enhanced efficacy and selectivity. In silico investigations, including molecular docking, molecular dynamics simulations, and MM/GBSA analysis, revealed stable binding of the synthesized compound within the VEGFR2 active site, supported by favorable binding free energy and key ligand-residue interactions.

A structurally diverse series of thieno[2,3-d]pyrimidine derivatives was rationally designed and synthesized through a multistep diversification strategy enabling systematic modulation of molecular architecture, conformational flexibility, and electronic distribution within a unified heterocyclic framework. The synthetic route involved sequential functionalization reactions to generate derivatives incorporating amino, acetanilide, azomethine, and fused dipyrimidine motifs. Structural elucidation was achieved using IR, NMR, and HRMS analyses. Beyond synthetic accessibility, the study focused on understanding how controlled structural modifications influence molecular behavior, electronic properties, and target-binding characteristics. Computational investigations including molecular docking, molecular dynamics simulations, MM/GBSA calculations, frontier molecular orbital analysis, molecular electrostatic potential mapping, and NBO analysis were performed against dihydrofolate reductase (DHFR). Comparative docking analysis of compounds 10-12 revealed that subtle structural transformations significantly affect binding affinity, interaction patterns, and conformational stability within the catalytic pocket. Compound 10 exhibited the most favorable binding profile (Delta G = -9.8 kcal/mol) and strongest interaction stability, supported by low RMSD and RMSF values, reduced SASA and radius of gyration fluctuations, and a favorable MM/GBSA binding free energy (Delta G_bind = -42.12 kcal/mol). The presence of the free 5-amino group and acetanilide moiety in compound 10 enabled cooperative hydrogen-bonding and hydrophobic interactions with key residues including Thr46, Ser49, Leu20, Leu28, Ile31, and Phe92. In contrast, structural rigidification in compound 11 and replacement of the amino functionality in compound 12 altered residue stabilization patterns and weakened interaction networks. DFT calculations further demonstrated that compound 10 possesses the narrowest HOMO-LUMO gap, highest softness, and strongest electrophilic character among the investigated derivatives, indicating enhanced electronic adaptability and reactivity. Antibacterial evaluation showed moderate strain-selective activity that correlated with the observed structure-dependent interaction behavior. Collectively, these findings establish the thieno[2,3-d]pyrimidine scaffold as a valuable platform for structure-guided molecular engineering and provide mechanistic insight into the relationship between molecular architecture, electronic properties, and biological function.

Three-layer thicknesses (\({T}_{1 }= 50\), \({T}_{2 }= 75\) and \({T}_{3 }= 100\) nm) of 1,2-bis(diphenylphosphino)ethyl tungsten tetracarbonyl methyl red (DPE-W-MR) were deposited onto the CuO thin film (50 nm) to produce DPE-W-MR/CuO di-layer thin films by sol–gel spin-coating technique. The composition and the chemical structure of the as-prepared thin films were characterized using various techniques including elemental analysis, Fourier transform infrared spectroscopy, \(^{1}\hbox {H}\)-NMR and X-ray diffraction (XRD). Scanning electron microscopy was used to investigate the size and shape of the CuO nanoparticles and the fabricated thin films. The films are crystalline as evidenced by the XRD pattern and DPE-W-MR has an orthorhombic crystal system. The crystallite size was calculated from an analysis of the line broadening features using the Scherrer formula; the average crystallite sizes of DPE-W-MR/CuO di-layer thin films are 52.92, 56.24 and 72.26 nm for \({T}_{1}\), \({T}_{2}\) and \({T}_{3}\), respectively. Thermogravimetric analysis and the thermal curve of DPE-W-MR complex were studied. Optical properties of DPE-W-MR/CuO di-layer thin films are discussed. The optical band gap energies of DPE-W-MR di-layer thin films/CuO decreased (2.25, 2.1 and 1.88 eV) as the film thickness increased (from \({T}_{1}\) to \({T}_{3})\). Based on the optical results and the quantum confinement effects, the DPE-W-MR/CuO di-layer thin films may be candidates as semiconductor materials for optoelectronic devices.

Selenopyrimidine compounds, though less explored than their thieno[2,3-d]pyrimidine counterparts, exhibit significant potential as multifunctional agents. In this study, a series of novel pyrimidoselenolo[2,3-d]pyrimidine compounds was synthesized using a straightforward methodology. The structural characterization of the compounds was performed using elemental analyses, FT-IR, 1H NMR, and 13C NMR spectroscopy. Their antimicrobial activities were evaluated using the agar well diffusion method against various fungal and bacterial strains, with minimum inhibitory concentrations (MICs) compared to ciprofloxacin and ketoconazole as standards. Compounds with phenyl substituents displayed superior antibacterial and antifungal activities, while amino carboxamide derivatives showed comparatively lower efficacy. Additionally, the luminescence of selected molecules was explored in DMSO solutions and the solid state. Compounds exhibited strong absorption up to 450 nm and concentration-dependent emission behavior, with a clear red shift in emission spectra owing to the molecular aggregation. DFT calculations revealed significant changes in the structure of the ground and excited states, providing insights into the observed luminescence behavior. Molecular docking studies revealed a high affinity of target compounds to topoisomerase II enzyme. All target compounds were predicted to have acceptable physicochemical and pharmacokinetic parameters. Our findings feature the dual potential of selenopyrimidine derivatives as effective antimicrobial agents and promising candidates for luminescent applications. Thanks to combining biocompatibility and emission properties to present these compounds as possible candidates for biological applications such as bioimaging and bioprobes.

Thiadiazole, a bioisostere of pyrimidine and oxadiazole, has attracted considerable attention due to its diverse pharmacological applications. In this study, two thiadiazole derivatives were synthesized from 2-amino-5-mercapto-1,3,4-thiadiazole and isolated in excellent yields, demonstrating the practicality of the synthetic method. To evaluate their biological potential building on the reported activity of this skeleton, the synthesized compounds were tested for antimicrobial activity against a panel of pathogenic microorganisms, including Pseudomonas aeruginosa, Candida albicans, and Aspergillus brasiliensis. To further rationalize the observed activities, molecular docking studies were performed to investigate the binding interactions of the compounds with key microbial targets. Complementary molecular dynamics simulations were employed to assess the stability and dynamic behavior of the ligand–receptor complexes. The results revealed that the thiadiazole derivatives exhibited promising antimicrobial activity, supported by strong binding affinities toward the target receptors. Overall, this multidisciplinary approach highlights the potential of thiadiazoles as antimicrobial pharmacophores and provides valuable insights for the design and development of novel therapeutic agents.

Abstract In this study, new tetrahydroisoquinoline compounds were synthesized by reaction of 7-Acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8- (3-nitrophenyl or 4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones with methyl iodide, chloro acetonitrile, ethyl chloroacetate to produce compounds 3–5 and reacted with N-arylchloroacetamides reagents to gave tetrahydroisoquinolin-3-ylthio) acetamides compounds 6a–c, 8a–b which can cyclized to 6,7,8,9-tetrahydrothieno[2,3-c]Isoquinoline-2-carboxamides compounds 7a–c, 9a–b. Also react with N-(benzthiazol-2-yl)-2-chloroacetamideto give compound 10. The structures of all newly synthesized compounds were characterized by elemental and spectral analyses. Also, most of the synthesized compounds were evaluated for their anticancer activities aganist MCF7 and HEPG2 cell lines. From the result we found that the most active compound against the MCF7 cell lines was compound 8b, and the most active compound against HEPG2 cell lines was compound 3. Then the effects of compound 3 on the HEPG2 cell line was investigated using an apoptotic Annexin V-FITC test and flow cytometry. Compound 3 induced a 59-fold increase in HEPG2 cell line apoptosis and cell cycle arrested at the G0-G1, G2/M phases. Moreover, the molecular docking study was applied and the result showed that compounds 8b bind to the RET enzyme with binding energies of − 6.8 kcal/mol in comparison with standard alectinib, which exhibits a binding energy of − 7.2 kcal/mol. Compound 3 can bind with HSP 90 with a binding energy (ΔG) of − 6.8 kcal/mol, which was comparable to the standard Onalespib (− 7.1 kcal/mol). Graphical Abstract

In this work 7-Acetyl-4-cyano-1, 6-dimethyl-6-hydroxy-8-(2-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thione compound 2 was synthesized and used as starting materials. Subsequently, Compounds 3–7 were produced through its reaction with ethyl iodide, ethyl chloroacetate, chloroacetonitrile, and chloroacetaldehyde. Additionally, compound 2 and 2-chloroacetamide were heated in ethanol with sodium acetate trihydrate present, resulting in the formation of 3-Substituted methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 9a–d, respectively. Similarly, compounds 2 and N-(1-naphthyl)-2-chloroacetamide reacted to produce high yields of the equivalent N-(1-naphthyl)-(5,6,7,8-tetrahydroiso-quinolin-3-ylthio)acetamides 9e. Compounds 9a–e were cyclized into their 10a and d. Using elemental analysis and spectral data (FT-IR, 1H NMR, and 13C NMR). All newly synthesized compounds were described. The anticancer activity of the produced compounds was also assessed against eight cell lines at one spot concentration and one normal human skin fibroblast cell line HSF. Then determine the IC50 of our drugs against two specific cell lines using various doses. Compound 3 is the most effective chemical against HEGP2, according to our research. Compound 9c was also the most effective compound against HCT116. For generally, the tested substances showed moderate anticancer activity, according to the data. The effects of compound 3 on the proliferation of HEGP2 cell lines were then investigated using an apoptotic Annexin V-FITC assay and flow cytometry. Compound 3 increased the HEGP2 cell line's apoptosis by 50 times and caused cell cycle arrest at the G2/M phase.

In this work, we synthesized new 5, 6, 7, 8-tetrahydroisoquinolines and 6, 7, 8, 9-tetrahydrothieno[2, 3-c]isoquinolines derivatives, and the structures of these new compounds were confirmed with different spectroscopic techniques. Furthermore, the anticancer activities of these compounds were assessed against eight tumor cell lines and one normal human skin fibroblast cell line (HSF). Subsequently, IC50 values of the synthesized compounds were determined for two specific cancer cell lines. Compound 3 exhibited the most potent antiproliferative activity against the HEPG2 cell line, whereas compound 9c demonstrated superior efficacy against the HCT116 cell line. Moreover, the mechanism of action for compound 3 on HEPG2 cells using flow cytometry and Annexin V-FITC apoptosis analysis was studied. Compound 3 caused cell cycle arrest at the G2/M with a 50-fold increase in apoptosis of the HEPG2 cell line. Finally, a molecular docking study was conducted to assess the inhibitory potential of compounds 3 and 7 against the RET enzyme. Results indicated that compounds 3 and 7 bind to the RET enzyme with binding energies of -5.2 and -5.6 kcal/mol, respectively. Although these values suggest inhibitory activity, they are less potent than the standard inhibitor, alectinib, which exhibits a binding energy of -7.2 kcal/mol.

In this study, 7-Acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8- (3-nitrophenyl or 4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a-b were synthesized and used as starting materials. Thus, compounds 2a-b were reacted with methyl iodide, ethyl chloroacetate, by heating in ethanol in the presence of sodium acetate trihydrate to give 3-substituted methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 3, 4, respectively. In a similar manner, the reaction of compounds 2a-b with N-arylchloroacetamides5a-c afforded the corresponding N-aryl-(5,6,7,8-tetrahydroiso-quinolin-3-ylthio) acetamides 6a-c in excellent yields. In contrast, the reaction of 3b with N-(benzthiazol-2-yl)-2-chloroacetamide (12)under the same (above) conditions yielded 1-amino-N-(benzthiazol-2-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamide13.Cyclization of compounds 6a-c into their 7a-cwas performed by heating in ethanol containing a catalytic amount of sodium ethoxide. The structures of all newly synthesized compounds were characterized by elemental and spectral analyses. Also, most of the synthesized compounds were evaluated for their anticancer activity in MCF7 andHEGP2 cell lines.The most potent compound against theMCF7 cell lines was compound 9b, and the most potent against HEGP2 cell lines was compound 3. Then the effects of compound 3 on the proliferation of HEPG2 cell lines was investigated using an apoptotic Annexin V-FITC test and flow cytometry. Compound 3 induced a 59-fold increase in HEPG2 cell line apoptosis and cell cycle arrested at the G0-G1, G2/M phases.

In this study, we synthesized new 5,6,7,8-tetrahydroisoquinolines and 6,7,8,9-tetrahydrothieno[2,3- c ]isoquinolines based on 4-( N , N -dimethylamino)phenyl moiety as expected anticancer and/or antioxidant agents. The structure of all synthesized compounds were confirmed by spectral date (FT-IR, 1 H NMR, 13 C NMR) and elemental analysis. We evaluated the anticancer activity of these compounds toward two cell lines: A459 cell line (lung cancer cells) and MCF7 cell line (breast cancer cells). All tested compounds showed moderate to strong anti-cancer activity towards the two cell lines. Compound 7e exhibited the most potent cytotoxic activity against A549 cell line (IC 50 : 0.155 µM) while compound 8d showed the most potent one against MCF7 cell line (IC 50 : 0.170 µM) in comparison with doxorubicin. In addition, we examined the effect of compounds 7e and 8d regarding the growth of A549 and MCF7 cell lines, employing flow cytometry and Annexin V-FITC apoptotic assay. Our results showed that compound 7e caused cell cycle arrest at the G2/M phase with a 79-fold increase in apoptosis of A459 cell line. Moreover, compound 8d caused cell cycle arrest at the S phase with a 69-fold increase in apoptosis of MCF7 cell line. Furthermore, we studied the activity of these compounds as enzyme inhibitors against several enzymes. Our findings by docking and experimental studies that compound 7e is a potent CDK2 inhibitor with IC 50 of 0.149 µM, compared to the Roscovitine control drug with IC 50 of 0.380 µM. We also found that compound 8d is a significant DHFR inhibitor with an IC 50 of 0.199 µM, compared to Methotrexate control drug with IC 50 of 0.131 µM. Evaluation of the antioxidant properties of ten compounds was also studied in comparison with Vitamin C. Compounds 1 , 3 , 6 , 7c and 8e have higher antioxidant activity than Vitamin C which mean that these compounds can used as potent antioxidant drugs. Graphical Abstract

In this study, new tetrahydrosoquinoline compounds were synthesized by reacted with methyl iodide, chloro acetonitrile, ethyl chloroacetate, N-arylchloroacetamides N-and (benzthiazol-2-yl)-2-chloroacetamide reagents to gave tetrahydroiso-quinolin-3-ylthio) acetamides (5a-c) which can cyclized to tetrahydroiso-quinolin-3-ylthio) acetamides (6a-c) in excellent yields. The structures of all newly synthesized compounds were characterized by elemental and spectral analyses. Also, most of the synthesized compounds were evaluated for their anticancer activity in MCF7 and HEPG2 cell lines. From the result we found that the most potent compound against the MCF7 cell lines was compound 9b, and the most active against HEPG2 cell lines was compound 3. Then the effects of compound 3 on the HEPG2 cell line was investigated using an apoptotic Annexin V-FITC test and flow cytometry. Compound 3 induced a 59-fold increase in HEPG2 cell line apoptosis and cell cycle arrested at the G0-G1, G2/M phases. Moreover, the molecular docking study was applied and the result showed that compounds 9b bind to the RET enzyme with binding energies of -6.8 kcal/mol in comparison with standard alectinib, which exhibits a binding energy of -7.2 kcal/mol. Compound 3 can bind with HSP 90 with a binding energy (ΔG) of -6.8 kcal/mol, which is comparable to the standard Onalespib (-7.1 kcal/mol).

This research paper embarks on an interdisciplinary exploration encompassing synthetic chemistry, pharmacology, and computational biology. The development of novel anti-inflammatory agents is an imperative endeavor within pharmaceutical research. Pyrimidines and thienopyrimidines are class of heterocyclic compounds that have gained prominence for their diverse pharmacological properties, including potential anti-inflammatory effects. When augmented with an indole moiety, these compounds exhibit structural diversity that can profoundly influence their biological activities. The integration of computational biology specifically molecular docking, plays a crucial role in predicting and understanding the binding interactions between these compounds and select protein targets associated with inflammatory pathways. This computational approach expedites the screening of potential drug candidates and elucidates the molecular underpinnings of their anti-inflammatory actions. Pyrimidine and thienopyrimidines tethering indole scaffold were obtained according to our reported methods. Subsequently, in vivo evaluation of anti-inflammatory is indispensable to gauge the anti-inflammatory potential of these compounds and establish structure-activity relationships. The experimental and computational biology studies of the target indole-pyrimidines hybrids revealed that these compounds can serve as anti-inflammatory agents. This paper can potentially open new avenues for therapeutic strategies against inflammation-associated disorders. The synergy of synthetic innovation, pharmacological evaluation, and computational insights offers a holistic approach to advance our understanding of pyrimidines with an indole moiety as potential agents for mitigating inflammation.

Using the Sol-Gel spin coating method, a new [NiO-Inulin] nanocomposite in powder form was created as a thin film. The characterization of [NiO-Inulin]C has been performed with a variety of techniques, including Fourier Transform Infrared (FT-IR), Ultraviolet-Visible spectroscopy (UV-Vis), scanning electron microscopy (SEM), Xray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), and Transmission electron microscopy (TEM). FT-IR displays the characteristic bands of [NiO-Inulin]C with low intensities and a small shifting of the bands. In SEM, we observed the thymol blue dye (TB) was heavily absorbed by [NiO-Inulin]C and generated a coating of TB material on their surface. Again, XRD show the average crystallite sizes of inulin and [NiO-Inulin]C which were calculated as (19 and 33.5) nm, respectively. The shape of the nanocomposite is seen in the TEM picture as spherical shapes with particle sizes of 18 nm. It has been studied spectrophotometrically how [NiOInulin]C removes thymol blue (TB). It was investigated how variables including contact time, [TB], [NiO-Inulin]C dosage, temperature, and dye solution pH affected the results. So, the observed highest values of removal efficiency in case of influence of pH and [TB] are 52.03 and 86.46%, respectively. Models of the Freundlich and Langmuir isotherms were used to show how the adsorption equilibrium occurred. From experimental results the type of adsorption is endothermic process and occurs spontaneously.

The powder form of the new indole derivative 4-(((3-chloro-1H-indol-2-yl) methylene) amino) phenol [Indol4Ap] was synthesized and subsequently converted to a thin film [Indol-4Ap]TF using the Sol-Gel spin coating technique. Numerous characterization techniques, including Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and ultraviolet-visible (UV-Vis) optical spectroscopy were used to characterize [Indol-4Ap]TF. Additionally, using density functional theory (DFT), optimization tvia TD-DFTD/ Mol3 and Cambridge Serial Total Energy Bundle (TD-FDT/CASTEP) was developed. The DFT calculations accurately matched the observed NMR and FTIR spectra and validated the molecular structure of the examined materials. The average crystallite size of [Indol-4Ap]TF, as determined by XRD calculations, is 12.02 nm. The optical properties of the films were determined using optical absorbance spectrophotometric measurements in the 200-800 nm wavelength range. The optical energy bandgaps computed using Tauc's equation for the [Indol4Ap]TF are 3.152 and 2.751 eV, respectively. Whereas the [Indol-4Ap]iso has a bandgap of 3.074 eV as determined by TD-DFT/DMol3. The optical characteristics predicted by CASTEP in TD-DFT are in excellent agreement with the experimental values. The investigated compound has a large optical energy bandgap which is advantageous for some energy storage applications.

NiONPs was synthesized from Ficus Nitida plant under control conditions and which is considerably efficient for removal of dyes from wastewater. The obtained NiONPs was identified by Fourier transform infrared spectra (FTIR), Scanning electron microscopy (SEM), X-ray diffraction (XRD), Energy dispersive xray spectroscopy (EDX), Transmission electron microscopy (TEM) analyses and surface area. The removal of toxic thymol sulfone phthalein (TSP) dye by an efficient adsorbent NiONPs has been investigated spectrophotometrically. Variables such as contact time, initial dye concentration, adsorbent dose, temperature and pH of dye solution were studied. Langmuir and Freundlich isotherm models were used to illustrate the equilibrium of the adsorption. The correlation coefficient values of Langmuir and Freundlich equations were found to be in good agreement. A pseudo-second-order mechanism governs the absorption of TSP onto NiONPs. A spontaneous and exothermic process, adsorption was a spontaneous process. In addition, the thermodynamic parameters have been analyzed, and an appropriate reaction mechanism has been presented and discussed in this paper. (C) 2022 Elsevier B.V. All rights reserved.

2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)acetophenone (2) was synthesized by the reaction of 3-cyano-4,6-distyrylpyridin-2(1H)-thione (1) with an alkylating agent, phenacyl bromide in the presence of fused sodium acetate and ethanol. Compound 2 underwent Thorpe -Ziegler cyclization upon heating in ethanolic sodium ethoxide solution to yield the target, 3-amino-2-benzoyl-4,6-distyrylthieno[2,3-b]pyridine (3). Elemental and spectral characterizations of the newly synthesized compounds 2 and 3 have been achieved. Both compounds 2 and 3 exhibited significant insecticidal activities after treated for 24 and 48 h compared with the reference compound, acetamiprid, when screened for their insecticidal activity against the nymphs and adults of cowpea aphid, Aphis craccivora Koch. Therefore, the results obtained are very promising, and accentuate on the importance of such heterocyclic pyridine compounds as efficient pesticides.

Regioselective cyclocondensation of 2,4-diacetyl-5-hydroxy-5-methyl-3-(3-nitrophenyl/4-nitrophenyl)cyclohexanones 1a,b with cyanothioacetamide afforded the corresponding 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(3- and -4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a,b. Reaction of compounds 2a,b with ethyl iodide, 2-chloroacetamide (4a), or its N-aryl derivatives 4b-e in the presence of sodium acetate trihydrate gave 3-ethylthio-5,6,7,8-tetrahydroisoquinoline 3 and (5,6,7,8-tetrahydroisoquinolin-3-ylthio)acetamides 5a-i, respectively. Cyclization of compounds 5b-d,f,g into their isomeric 1-amino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamides 6b-d,f,g was achieved by heating in ethanol containing a catalytic amount of sodium carbonate. Structures of all synthesized compounds were characterized on the basis of their elemental analyses and spectroscopic data. The crystal structure of 5,6,7,8-tetrahydroisoquinoline 5d was determined by X-ray diffraction analysis. In addition, the biological evaluation of some synthesized compounds as anticancer agents was performed, and only six compounds showed moderate to strong activity against PACA2 (pancreatic cancer cell line) and A549 (lung carcinoma cell line). Moreover, the antioxidant properties of most synthesized compounds were examined. The results revealed high antioxidant activity for the most tested compounds.