Synthesis of Bis-thiazoles Tethered 1,4-Dihydropyridine and Pyridine Linkers via Simple Oxidation and their Molecular Docking as VEGFR -TK Inhibitors.

AIM: In this study, a neoteric and expedient oxidation method is applied for a variety of Hantzsch 1,4-dihydropyridine derivatives such as 1,4-dihydro- 2,6-dimethyl-3,5-diacetylpyridine, 3,5-bis-hydrazono--2,6-dimethyl-1,4-dihydropyridine, and 3,5-bis-thiazoly-2,6-dimethyl-1,4-dihydro pyridine. METHOD: This simple oxidation is based upon the in situ generation of nitrous acid from an aqueous sodium nitrite and acetic acid mixture and could be used to downgrade costs, sustain resources, and minimize chemical wastes. Also, a molecular modeling strategy was used to study the mechanism of action for various derivatives of bis-hydrazinylidene- thiazole as the protein Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor through evaluating their binding scores and modes compared with Sorafenib as a reference standard. RESULT: The results revealed that the interaction of hydrazinylidene and thiazole as an anticancer Tyrosine Kinase inhibitor has been improved. CONCLUSION: Additionally, the compounds exhibiting the highest activity were assessed for their potential anticancer effects against HepG-2, MCF-7, and WI-38 cells, and the outcomes demonstrated encouraging activity against cancer.

A Literature Review Focusing on the Antiviral Activity of [1,2,4] and [1,2,3]-triazoles.

Out of a variety of heterocycles, triazole scaffolds have been shown to play a significant part in a wide array of biological functions. Many drug compounds containing a triazole moiety with important antimicrobial, anticancer and antidepressant properties have been commercialized. In addition, the triazole scaffold exhibits remarkable antiviral activity either incorporated into nucleoside analogs or non-nucleosides. Many synthetic techniques have been produced by scientists around the world as a result of their wide-ranging biological function. In this review, we have tried to summarize new synthetic methods produced by diverse research groups as well as provide a comprehensive description of the function of [1,2,4] and [1,2,3]-triazole derivatives as antiviral agents. Antiviral triazole compounds have been shown to target a wide variety of molecular proteins. In addition, several strains of viruses, including the human immunodeficiency virus, SARS virus, hepatitis B and C viruses, influenza virus, Hantavirus, and herpes virus, were discovered to be susceptible to triazole derivatives. This review article covered the reports for antiviral activity of both 1,2,3- and 1,2,4-triazole moieties up to 2022.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents.

A novel set of thiazolylhydrazonothiazoles bearing an indole moiety were synthesized by subjection reactions of carbothioamide derivative and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity of the synthesized compounds was evaluated against the colon carcinoma cell line (HCT-116), liver carcinoma cell line (HepG2), and breast carcinoma cell line (MDA-MB-231), and demonstrated encouraging activity. Furthermore, when representative products were assessed for toxicity against normal cells, minimal toxic effects were observed, indicating their potential safety for use in pharmacological studies. The mechanism of action of the tested products, as inhibitors of the epidermal growth factor receptor tyrosine kinase domain (EGFR TK) protein, was suggested through docking studies that assessed their binding scores and modes, in comparison to a reference standard (W19), thus endorsing their anticancer activity.

Green Synthetic Approaches of 2-Hydrazonothiazol-4(5H)-ones Using Sustainable Barium Oxide-Chitosan Nanocomposite Catalyst.

The diverse applications of metal oxide-biopolymer matrix as a nanocomposite heterogenous catalyst have caused many researches to scrutinize the potential of this framework. In this study, a novel hybrid barium oxide-chitosan nanocomposite was synthesized through a facile and cost-effective co-precipitation method by doping barium oxide nanoparticles within the chitosan matrix at a weight percentage of 20 wt.% BaO-chitosan. A thin film of the novel hybrid material was produced by casting the nanocomposite solution in a petri dish. Several instrumental methods, including Fourier-transform infrared (FTIR), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD), were used to analyze and characterize the structure of the BaO-CS nanocomposite. The chemical interaction with barium oxide molecules resulted in a noticeable displacement of the most significant chitosan-specific peaks in the FTIR spectra. When the surface morphology of SEM graphs was analyzed, a dramatic morphological change in the chitosan surface was also discovered; this morphological change can be attributed to the surface adsorption of BaO molecules. Additionally, the patterns of the XRD demonstrated that the crystallinity of the material, chitosan, appears to be enhanced upon interaction with barium oxide molecules with the active sites, OH and NH2 groups, along the chitosan backbone. The prepared BaO-CS nanocomposite can be used successfully as an effective heterogenous recyclable catalyst for the reaction of N,N'-(alkane-diyl)bis(2-chloroacetamide) with 2-(arylidinehydrazine)-1-carbothioamide as a novel synthetic approach to prepare 2-hydrazonothiazol-4(5H)-ones. This new method provides a number of benefits, including quick and permissive reaction conditions, better reaction yields, and sustainable catalysts for multiple uses.

Synthesis and In Silico Study of Some New bis-[1,3,4]thiadiazolimines and bis-Thiazolimines as Potential Inhibitors for SARS-CoV-2 Main Protease.

A novel series of bis-[1,3,4]thiadiazolimines, and bis-thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1'-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α-haloketones, respectively. Docking studies were applied to test the binding affinity of the synthesized products against the Mpro of SARS-CoV-2. The best compound, 5h, has average binding energy (-7.50 ± 0.58 kcal/mol) better than that of the positive controls O6K and N3 (-7.36 ± 0.34 and -6.36 ± 0.31 kcal/mol). Additionally, the docking poses (H-bonds and hydrophobic contacts) of the tested compounds against the Mpro using the PLIP web server were analyzed.

Synthesis, Molecular Docking Study, and Cytotoxic Activity against MCF Cells of New Thiazole-Thiophene Scaffolds.

Investigating novel compounds that may be useful in designing new, less toxic, selective, and potent breast anticancer agents is still the main challenge for medicinal chemists. Thus, in the present work, acetylthiophene was used as a building block to synthesize a novel series of thiazole-bearing thiophene derivatives. The structures of the synthesized compounds were elucidated based on elemental analysis and spectral measurements. The cytotoxic activities of the synthesized compounds were evaluated against MCF-7 tumor cells and compared to a cisplatin reference drug, and against the LLC-Mk2 normal cell line using the MTT assay, and the results revealed promising activities for compounds 4b and 13a. The active compounds were subjected to molecular modeling using MOE 2019, the pharmacokinetics were studied using SwissADME, and a toxicity radar was obtained from the biological screening data. The results obtained from the computational studies supported the results obtained from the anticancer biological studies.

Chitosan-Strontium Oxide Nanocomposite: Preparation, Characterization, and Catalytic Potency in Thiadiazoles Synthesis.

Recently, Strontium oxide (SrO) nanoparticles (NPs) and hybrids outperformed older commercial catalysts in terms of catalytic performance. Herein, we present a microwave-assisted easy in situ solution casting approach for the manufacture of strontium oxide nanoparticles doped within a naturally occurring polymer, chitosan (CS), at varying weight percentages (2.5, 5, 10, 15, and 20 wt.% SrO/chitosan). To construct the new hybrid material as a thin film, the produced nanocomposite solutions were cast in petri dishes. The aim of the research was to synthesize these hybrid nanocomposites, characterize them, and evaluate their catalytic potential in a variety of organic processes. The strontium oxide-chitosan nanocomposites were characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), and scanning electron microscope (SEM) techniques. All the results confirmed the formation of chitosan-strontium oxide nanocomposite. FTIR spectrum of nanocomposite showed the presence of a characteristic peak of Sr-O bond. Furthermore, XRD revealed that SrO treatment increased the crystallinity of chitosan. The particle size was calculated using the Debye-Scherrer formula, and it was determined to be around 36 nm. The CS-SrO nanocomposite has been proven to be a highly efficient base promoter for the synthesis of 2-hydrazono [1,3,4]thiadiazole derivatives. To optimize the catalytic method, the reaction factors were investigated. The approach has various advantages, including higher reaction yields, shorter reaction durations, and milder reaction conditions, as well as the catalyst's reusability for several applications.

Synthesis and greener pastures biological study of bis-thiadiazoles as potential Covid-19 drug candidates.

A novel series of bis- (Abdelhamid et al., 2017, Banerjee et al., 2018, Bharanidharan et al., 2022)thiadiazoles was synthesized from the reaction of precursor dimethyl 2,2'-(1,2-diphenylethane-1,2-diylidene)-bis(hydrazine-1-carbodithioate) and hydrazonyl chlorides in ethanol under ultrasonic irradiation. Spectral tools (IR. NMR, MS, elemental analyses, molecular dynamic simulation, DFT and LUMO and HOMO) were used to elucidate the structure of the isolated products. Molecular docking for the precursor, 3 and ligands 6a-i to two COVID-19 important proteins Mpro and RdRp was compared with two approved drugs, Remdesivir and Ivermectin. The binding affinity varied between the ligands and the drugs. The highest recorded binding affinity of 6c with Mpro was (-9.2 kcal/mol), followed by 6b and 6a, (-8.9 and -8.5 kcal/mol), respectively. The lowest recorded binding affinity was (-7.0 kcal/mol) for 6 g. In comparison, the approved drugs showed binding affinity (-7.4 and -7.7 kcal/mol), for Remdesivir and Ivermectin, respectively, which are within the range of the binding affinity of our ligands. The binding affinity of the approved drug Ivermectin against RdRp recoded the highest (-8.6 kcal/mol), followed by 6a, 6 h, and 6i are the same have (-8.2 kcal/mol). The lowest reading was found for compound 3 ligand (-6.3 kcal/mol). On the other side, the amino acids also differed between the compounds studied in this project for both the viral proteins. The ligand 6a forms three H-bonds with Thr 319(A), Sr 255(A) and Arg 457(A), whereas Ivermectin forms three H-bonds with His 41(A), Gly143(A) and Gln 18(A) for viral Mpro. The RdRp amino acids residues could be divided into four groups based on the amino acids that interact with hydrogen or hydrophobic interactions. The first group contained 6d, 6b, 6 g, and Remdesivir with 1-4 hydrogen bonds and hydrophobic interactions 1 to 10. Group 2 is 6a and 6f exhibited 1 and 3 hydrogen bonds and 15 and 14 hydrophobic interactions. Group 3 has 6e and Ivermectin shows 4 and 3 hydrogen bonds, respectively and 11 hydrophobic interactions for both compounds. The last group contains ligands 3, 6c, 6 h, and 6i gave 1-3 hydrogen bonds and 6c and 3 recorded the highest number of hydrophobic interactions, 14 for both 6c and 6 h. Pro Tox-II estimated compounds' activities as Hepatoxic, Carcinogenic and Mutagenic, revealing that 6f-h were inactive in all five similar to that found with Remdesivir and Ivermectin. The drug-likeness prediction was carried out by studying physicochemical properties, lipophilicity, size, polarity, insolubility, unsaturation, and flexibility. Generally, some properties of the ligands were comparable to that of the standards used in this study, Remdesivir and Ivermectin.

Bio-Based (Chitosan-ZnO) Nanocomposite: Synthesis, Characterization, and Its Use as Recyclable, Ecofriendly Biocatalyst for Synthesis of Thiazoles Tethered Azo Groups.

In recent years, nanotechnology has become a considerable research interest in the area of preparation of nanocatalysts based on naturally occurring polysaccharides. Chitosan (CS), as a naturally occurring biodegradable and biocompatible polysaccharide, is successfully utilized as an ideal template for the immobilization of metal oxide nanoparticles. In this study, zinc oxide nanoparticles have been doped within a chitosan matrix at dissimilar weight percentages (5, 10, 15, 20, and 25 wt.% CS/ZnO) and have been fabricated by using a simple solution casting method. The prepared solutions of the nanocomposites were cast in a Petri-dish and were subsequently shaped as a thin film. After that, the structural features of the nanocomposite film have been studied by measuring the FTIR, SEM, and XRD analytical tools. FTIR spectra showed the presence of some changes in the major characteristic peaks of chitosan due to interaction with ZnO nanoparticles. In addition, SEM graphs exhibited dramatic morphology changes on the chitosan surface, which is attributed to the surface adsorption of ZnO molecules. Based on the results of the investigated organic catalytic reactions, the prepared CS/ZnO nanocomposite film (20 wt.%) could be a viable an effective, recyclable, and heterogeneous base catalyst in the synthesis of thiazoles. The results showed that the nanocomposite film is chemically stable and can be collected and reused in the investigated catalytic reactions more than three times without loss of its catalytic activity.

Potential COVID-19 Drug Candidates Based on Diazinyl-Thiazol-Imine Moieties: Synthesis and Greener Pastures Biological Study.

A novel series of 1-aryl-N-[4-phenyl-5-(arylazo)thiazol-2-yl)methanimines has been synthesized via the condensation of 2-amino-4-phenyl-5-arylazothiazole with various aromatic aldehydes. The synthesized imines were characterized by spectroscopic techniques, namely 1H and 13C-NMR, FTIR, MS, and Elemental Analysis. A molecular comparative docking study for 3a-f was calculated, with reference to two approved drugs, Molnupiravir and Remdesivir, using 7BQY (Mpro; PDB code 7BQY; resolution: 1.7 A°) under identical conditions. The binding scores against 7BQY were in the range of -7.7 to -8.7 kcal/mol for 3a-f. The high scores of the compounds indicated an enhanced binding affinity of the molecules to the receptor. This is due to the hydrophobic interactions and multi-hydrogen bonds between 3a-f ligands and the receptor's active amino acid residues. The main aim of using in silco molecular docking was to rank 3a-f with respect to the approved drugs, Molnupiravir and Remdesivir, using free energy methods as greener pastures. A further interesting comparison presented the laydown of the ligands before and after molecular docking. These results and other supporting statistical analyses suggested that ligands 3a-f deserve further investigation in the context of potential therapeutic agents for COVID-19. Free-cost, PASS, SwissADME, and Way2drug were used in this research paper to determine the possible biological activities and cytotoxicity of 3a-f.

Synthesis of Chitosan-La2O3 Nanocomposite and Its Utility as a Powerful Catalyst in the Synthesis of Pyridines and Pyrazoles.

Recently, the development of nanocatalysts based on naturally occurring polysaccharides has received a lot of attention. Chitosan (CS), as a biodegradable and biocompatible polysaccharide, is considered to be an excellent template for the design of a hybrid biopolymer-based metal oxide nanocomposite. In this case, lanthanum oxide nanoparticles doped with chitosan at different weight percentages (5, 10, 15, and 20 wt% CS/La2O3) were prepared via a simple solution casting method. The prepared CS/La2O3 nanocomposite solutions were cast in a Petri dish in order to produce the developed catalyst, which was shaped as a thin film. The structural features of the hybrid nanocomposite film were studied by FTIR, SEM, and XRD analytical tools. FTIR spectra confirmed the presence of the major characteristic peaks of chitosan, which were modified by interaction with La2O3 nanoparticles. Additionally, SEM graphs showed dramatic morphological changes on the surface of chitosan, which is attributed to surface adsorption with La2O3 molecules. The prepared CS/La2O3 nanocomposite film (15% by weight) was investigated as an effective, recyclable, and heterogeneous base catalyst in the synthesis of pyridines and pyrazoles. The nanocomposite used was sufficiently stable and was collected and reused more than three times without loss of catalytic activity.

Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (Mpro).

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (-8.1 ± 0.33 kcal/mol, -8.0 ± 0.35 kcal/mol, and -8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (-6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

Two decades of the synthesis of mono- and bis-aminomercapto[1,2,4]triazoles.

4-Amino-5-mercapto[1,2,4]triazole and its 3-substituted derivatives have proven to be of biological interest and provide access to a new class of biologically active heterocyclic compounds for biomedical applications. This study will be helpful for scientific researchers interested in the chemistry of bifunctional versatile compounds as it provides a collection of all the methods for the preparation of 3-substituted-4-amino-5-mercapto[1,2,4]triazoles with aliphatic, aromatic, and heterocyclic moieties during the period from 2000 to mid-2020.

Synthesis, characterization and application of copper oxide chitosan nanocomposite for green regioselective synthesis of [1,2,3]triazoles.

Chitosan copper (II) oxide nanocomposite was synthesized, characterized and used to synthesize [1,2,3]triazoles. Nanocomposite was characterized by using FTIR, XRD, FESEM, and EDS techniques, which reflected rough morphology. The powerful catalytic activity of hybrid nanocomposite was utilized to synthesize chalcones (3a-p) in relatively high yields (82%-98%) and multicomponent regio-selective cycloaddition of chalones, aryl halides (4), and sodium azide to afford the expected N-2-aryl[1,2,3]triazoles (5a-h) (80%-95% yield) rather than N-1-aryl[1,2,3]-triazoles (6a-h). The performance of nanomaterial was optimized by several variables. The capability of the nanocomposite was compared with previous work and the nanocomposite was found more efficient, economic and reproducible. The hybrid nanocomposite could be easily isolated form the reaction mixture and recycled four times without any significant loss of its catalytic activity. The reported catalyst is an inexpensive for good yields of the triazoles and may be used at industrial production for the reported compounds.

Chitosan-MgO Nanocomposite: One Pot Preparation and Its Utility as an Ecofriendly Biocatalyst in the Synthesis of Thiazoles and [1,3,4]thiadiazoles.

A chitosan-MgO hybrid nanocomposite was prepared using a simple chemical precipitation method and characterized using Fourier transform spectroscopy (FTIR), elemental analysis (EDX), and scanning electron microscopy (SEM). The nanocomposite was served as a powerful ecofriendly basic catalyst under microwave irradiation in the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 4a⁻j and 2-hydrazono[1,3,4]thiadiazoles 8a⁻d, incorporating a sulfonamide group. The structures of the synthesized products were elucidated by spectral data and elemental analyses. Also, their yield percentages were calculated using triethylamine (as a traditional catalyst) and chitosan-MgO nanocomposite (as a green recyclable catalyst) in a comparative study.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors.

2-(1-{4-[(4-Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was exploited as a starting material for the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 6a - 6j and 2-hydrazono[1,3,4]thiadiazoles 10a - 10d, incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.

Synthesis of New Bis-Spiropyrazoles as Antitumor Agents under Ultrasound Irradiation.

OBJECTIVE AND BACKGROUND: Hydrazonoyl halides were used as precursors for the synthesis of a new series of bis-spiropyrazoles via reaction with 3,5-diarylidene-piperidone derivatives under ultrasound irradiation. The products were secluded in good yield after short reaction periods. CONCLUSION: The anticancer activity of bis-spiropyrazoles against HepG2 (hepatic cancer), A549 (lung cancer) and CaCo2 (colon cancer) cell lines was screened. Three tested compounds 4b, 4c and 4f showed promising activity.

Rational design, synthesis, pharmacophore modeling, and docking studies for identification of novel potent DNA-PK inhibitors.

Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking of DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward DNA repair pathways. Hence, the search for potent and selective DNA-PK inhibitors has particularly considered state-of-the art and several series of inhibitors have been designed. In this article, a novel benchmark DNA-PK database of 43 compounds was built and described. Ligand-based approaches including pharmacophore and QSAR modeling were applied and novel models were introduced and analyzed for predicting activity test for DNA-PK drug candidates. Based upon the modeling results, we gave a report of synthesis of fifteen novel 2-((8-methyl-2-morpholino-4-oxo-4H-benzo[e][1,3]oxazin-7-yl)oxy)acetamide derivatives and in vitro evaluation for DNA-PK inhibitory and antiproliferative activities. These fifteen compounds overall are satisfied with Lipinski's rule of five. The biological testing of target compounds showed five promising active compounds 7c, 7d, 7f, 9e and 9f with micromolar DNA-PK activity range from 0.25 to 5µM. In addition, SAR of the compounds activity was investigated and confirmed that the terminal aryl moiety was found to be quite crucial for DNA-PK activity. Moreover flexible docking simulation was done for the potent compounds into the putative binding site of the 3D homology model of DNA-PK enzyme and the probable interaction model between DNA-PK and the ligands was investigated and interpreted.

Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation.

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.

Enaminones as building blocks for the synthesis of substituted pyrazoles with antitumor and antimicrobial activities.

Novel N-arylpyrazole-containing enaminones 2a,b were synthesized as key intermediates. Reactions of 2a,b with active methylene compounds in acetic acid in the presence of ammonium acetate afforded substituted pyridine derivatives 5a-d. Enaminones 2a,b also reacted with aliphatic amines such as hydrazine hydrate and hydroxylamine hydrochloride to give bipyrazoles 8a,b and pyrazolylisoxazoles 9a,b, respectively. On the other hand, treatment of 2a,b with a heterocyclic amine and its diazonium salt yielded the respective [1,2,4]triazolo[4,3-a]pyrimidines 12a,b and pyrazolylcarbonyl[1,2,4]triazolo-[3,4-c][1,2,4]triazines 14a,b. Moreover, 2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (17) was prepared via reaction of enaminone 2a with aminothiouracil (15). Cyclocondensation of 17 with the appropriate hydrazonoyl chlorides 18a-c gave the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones 21a-c. The cytotoxic effects of compounds 2b, 14a and 17 against human breast cell line (MCF-7) and liver carcinoma cell line (HEPG2) were screened and in both lines they showed inhibition effects comparable to those of 5-fluorouracil, used as a standard. The antimicrobial activity of some products chosen as representative examples was also evaluated.