Synthesis and Anti-Breast Cancer Potency of Mono- and Bis-(pyrazolyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine) Derivatives as EGFR/CDK-2 Target Inhibitors.

The target mono- and bis-(6-pyrazolyltriazolo-thiadiazine) derivatives 4a-c and 6a-d were synthesized using a straightforward protocol via reaction of 3-bromoacetylpyrazole 2 with 4-amino-s-triazole-3-thiols 3a-c and bis(4-amino-5-mercapto-s-triazol-3-yl)alkanes 5a-d, respectively. The bis(6-pyrazolyl-s-triazolo[3,4-b][1,3,4]thiadiazine) derivatives 8a,b and 10 were also constructed by reaction of the triazolo[3,4-b][1,3,4]thiadiazine-3-thiol 4c with the proper dibromo compounds 7a,b and 9, respectively. Structures of the new substances were determined by spectroscopic and analytical data. Compounds 4b, 4c, and 6a showed potent cytotoxicity against MCF-7 (IC50 = 3.16, 2.74, and 0.39 µM, respectively) and were safe against the MCF-10A cells. Compounds 4b, 4c, and 6a also showed promising dual EGFR and CDK-2 inhibition activities, particularly 6a was the most effective (IC50 = 19.6 and 87.9 nM, respectively), better than Erlotinib and Roscovitine. Compound 6a treatment induced EGFR and CDK-2 enzyme inhibition by 97.18% and 94.11%, respectively, at 10 µM (the highest concentration). Compound 6a notably induced cell apoptosis in MCF-7 cells, increasing the cell population by total apoptosis 43.3% compared to 1.29% for the untreated control group, increasing the cell population at the S-phase by 39.2% compared to 18.6% (control).

Synthesis of novel mono- and bis-pyrazolylthiazole derivatives as anti-liver cancer agents through EGFR/HER2 target inhibition.

3-Bromoacetyl-4-(2-naphthoyl)-1-phenyl-1H-pyrazole (6) was synthesized from 2-acetylnaphthalene and was used as a new key building block for constructing the title targets. Thus, the reaction of 6 with the thiosemicarbazones 7a-d and 9-11 afforded the corresponding simple naphthoyl-(3-pyrazolyl)thiazole hybrids 8a-d and 12 ~ 14. The symmetric bis-(2-naphthoyl-pyrazol-3-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)alkanes 18a-c and 21a-c were similarly synthesized from reaction of 6 with the appropriate bis-thiosemicarbazones 17a-c and 19a-c, respectively. The synthesized two series of simple and symmetrical bis-molecular hybrid merging naphthalene, thiazole, and pyrazole were evaluated for their cytotoxicity. Compounds 18b,c and 21a showed the most potent cytotoxicity (IC50 = 0.97-3.57 µM) compared to Lapatinib (IC50 = 7.45 µM). Additionally, they were safe (non-cytotoxic) against the THLE2 cells with higher IC50 values. Compounds 18c exhibited promising EGFR and HER-2 inhibitory activities with IC50 = 4.98 and 9.85 nM, respectively, compared to Lapatinib (IC50 = 6.1 and 17.2 nM). Apoptosis investigation revealed that 18c significantly activated apoptotic cell death in HepG2 cells, increasing the death rate by 63.6-fold and arresting cell proliferation at the S-phase. Compound 18c upregulated P53 by 8.6-fold, Bax by 8.9-fold, caspase-3,8,9 by 9, 2.3, and 7.6-fold, while it inhibited the Bcl-2 expression by 0.34-fold. Thereby, compound 18c exhibited promising cytotoxicity against EGFR/HER2 inhibition against liver cancer.

Anticancer therapeutic potential of benzofuran scaffolds.

Benzofuran moiety is the main component of many biologically active natural and synthetic heterocycles. These heterocycles have unique therapeutic potentials and are involved in various clinical drugs. The reported results confirmed the extraordinary inhibitory potency of such benzofurans against a panel of human cancer cell lines compared with a wide array of reference anticancer drugs. Several publications about the anticancer potencies of benzofuran-based heterocycles were encountered. The recent developments of anticancer activities of both natural and synthetic benzofuran scaffolds during 2019-2022 are thoroughly covered. Many of the described benzofurans are promising candidates for development as anticancer agents based on their outstanding inhibitory potency against a panel of human cancer cells compared with reference anticancer drugs. These findings encourage medicinal chemists to explore new areas to improve human health and reduce suffering.

Novel bis-amide-based bis-thiazoles as Anti-colorectal Cancer Agents Through Bcl-2 Inhibition: Synthesis, In Vitro, and In Vivo studies.

BACKGROUND: Some heterocycles having bisamide linkage are receiving much interest due to their remarkable biological potencies and they are naturally occurring. Some bisamides and thiazole derivatives were found to inhibit the protein levels of Bcl-2 significantly. This prompted us to synthesize new bis(heterocyclic) derivatives having bisamide function to explore their anti-cancer activities. METHODS: Novel bis-amide-based bis-thiazoles and thiadiazoles were synthesized by reaction of a new bisthiosemicarbazone with a variety of hydrazonoyl chlorides, a-chloroacetylacetone and haloacetic acid derivatives. Most of the synthesized derivatives were tested for colorectal (HCT-116) and breast (MCF-7) cell lines using the MTT assay, with the apoptotic investigation through flow cytometric and RT-PCR analyses. RESULTS: Some derivatives were found to be highly cytotoxic against HCT-116 cells with an IC50 range of (10.44-13.76 µM) compared to 5-fluorouracil (5-FU) (IC50 = 11.78 µM). One product significantly stimulated apoptotic colorectal cancer cell death by 27.24-fold (50.13% compared to control 1.84%) by arresting the cell cycle at the G2/M phase. The obtained results revealed that compound 7f was more cytotoxic against HCT-116 cells than 5-FU. Compound 7f remarkably enhanced apoptotic colorectal cancer cell death and upregulated the propapoptotic genes (P53, BAX and Capases-3,-8,-9) and downregulated the anti-apoptotic gene, B-cell lymphoma 2 (Bcl-2). In vivo study exhibited that 7f-treatment caused tumor inhibition ratio (TIR%) of 50.45% compared to 54.86% in the 5-FU treatment, with a significant reduction in tumor mass and volume. The anti-tumor activity of compound 7f was accompanied by ameliorated hematological and biochemical analyses, histopathological improvement in treated liver tissues, and the immunohistochemical staining revealed Bcl-2 inhibition in agreement with the in vitro results. CONCLUSION: Compound 7f is an interesting candidate for further development as a chemotherapeutic anti-cancer agent.

Design and synthesis of new bis(1,2,4-triazolo[3,4-b][1,3,4]thiadiazines) and bis((quinoxalin-2-yl)phenoxy)alkanes as anti-breast cancer agents through dual PARP-1 and EGFR targets inhibition.

A number of new 1,ω-bis((acetylphenoxy)acetamide)alkanes 5a-f were prepared then their bromination using NBS furnished the novel bis(2-bromoacetyl)phenoxy)acetamides 6a-f. Reaction of 6a-f with 4-amino-5-substituted-4H-1,2,4-triazole-3-thiol 7a-d and with o-phenylenediamine derivatives 9a and b afforded the corresponding bis(1,2,4-triazolo[3,4-b][1,3,4]thiadiazine) derivatives 8a-l and bis(quinoxaline) derivatives 10a-e in good yields. The cytotoxicity of the synthesized compounds as well as apoptosis induction through PARP-1 and EGFR as molecular targets was evaluated. Three compounds, 8d, 8i and 8l, exhibited much better cytotoxic activities against MDA-MB-231 than the drug Erlotinib. Interestingly, compound 8i induced apoptosis in MDA-MB-231 cells by 38-fold compared to the control arresting the cell cycle at the G2/M phase, and its treatment upregulated P53, Bax, caspase-3, caspase-8, and caspase-9 gene levels, while it downregulated the Bcl2 level. Compound 8i exhibited promising dual enzyme inhibition of PARP-1 (IC50 = 1.37 nM) compared to Olaparib (IC50 = 1.49 nM), and EGFR (IC50 = 64.65 nM) compared to Erlotinib (IC50 = 80 nM). These results agreed with the molecular docking studies that highlighted the binding disposition of compound 8i inside the PARP-1 and EGFR protein active sites. Hence, compound 8i may serve as a potential anti-breast cancer agent.

Regulatory Effect of Adipose-Derived Mesenchymal Stem Cells and/ or Acitretin on Adam10 Gene in Alzheimer's Disease Rat Model.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by progressive cognitive deterioration. All recent therapeutic strategies tend to inhibit the generation of the Aß peptide. These approaches tend to mediate both α - and γ -secretases to undergo the nonamyloidogenic pathway. ADAM10 is the main α-secretase that cleaves APP, and it is regulated by the metabolic product of vitamin A (retinoic acid), which is being widely used recently in AD research as a target for treatment. Mesenchymal stem cells (MSCs) are also used recently as a promising regenerative therapy for AD. OBJECTIVES: The present study aimed to: (1) study the effect of MSCs with/without acitretin on the regulation of Adam10 gene expression in AlCl3-induced AD rat model, and (2) validate the hypothesis that AD is a time-dependent progressive disease that spreads spontaneously even after the stopping of exposure to AlCl3. METHODS: The experimental work has been designed to include three successive phases; AlCl3 induction phase (I), AlCl3 withdrawal phase (W), and therapeutic phase (T). Forty-five male albino Wistar rats were randomly divided into 2 main groups: the control (C) group (15 rats) and AD group (30 rats). The therapeutic potential of MSCs with/without acitretin has been evaluated at behavioral, physiological, molecular, and histopathological levels. RESULTS: Among the three therapeutic groups, combined administration of both MSC and acitretin showed the best compensatory effects on most of the measured parameters. CONCLUSION: The present study approved that AD is a time-dependent progressive disease which spreads spontaneously without more AlCl3 exposure.

Inhibitory activities of bipyrazoles: a patent review.

INTRODUCTION: Bipyrazole is constituted from two pyrazole units either in their fully aromatic or partially hydrogenated forms. Pyrazoles are widely available in pharmaceutical and agrochemical products. Some pyrazoles are essential parts of commercial drugs in the market. This inspired us to collect the pharmacological activities of bipyrazoles that have potential therapeutic behaviors in several biological aspects but none of them were included in commercial drugs. AREAS COVERED: This review covers all biological and pharmacological potentials of bipyrazole derivatives during 2010-2021. The topics of this review comprised anticancer, antioxidant, anti-inflammatory, antimicrobial, antitubercular, antimalarial, insecticidal activities as well as enzymatic inhibitions. EXPERT OPINION: Bipyrazoles demonstrated a wide array of potent activities against various diseases such as anticancer, antitubercular, anti-inflammatory, and antimicrobial activities. Those are of great benefits for medicinal researchers to develop promising building blocks of bipyrazoles for treatment of diseases. The SAR studies showed that metallated bipyrazoles had better biological activities than bipyrazole ligands. For example, gold(III) and iridium(II) complexes of bipyrazoles were proved to be anticancer agents, and copper(I) as well as silver(I) complexes had excellent antibacterial activities. Several bipyrazoles were reported as antimalarial inhibitors better than chloroquine, the possible COVID-19 drug.

Inhibitory Activities of Pyrazolo-Oxazine Heterocyclic Derivatives.

Despite several reports and reviews addressing the biological significance of pyrazoles and oxazines, no comprehensive work on the pyrazolo oxazine fused ring system has been published so far. We report all biological evaluations on pyrazolo-oxazine derivatives in this mini-review to provide an avenue for medicinal and pharmacological researchers to conduct further in-depth exploration.

Novel Bis-Thiazole Derivatives: Synthesis and Potential Cytotoxic Activity Through Apoptosis With Molecular Docking Approaches.

A series of bis-thiazoles 5a-g were synthesized from bis-thiosemicarbazone 3 with hydrazonoyl chlorides 4a-g. Reaction of 3 with two equivalents of α-halocarbonyl compounds 6-8, 10, and 12a-d afforded the corresponding bis-thiazolidines 9, 11, and 13a-d, respectively. Condensation of bis-thiazolidin-4-one 9 with different aromatic aldehydes furnished bis-thiazolidin-4-ones 14a-d. Compounds 5a-g, 9, and 13a,c,d were screened in vitro for their cytotoxic activities in a panel of cancer cell lines. Compounds 5a-c, 5f-g, and 9 exhibited remarkable cytotoxic activities, especially compound 5c with potent IC50 value 0.6 nM (against cervical cancer, Hela cell line) and compound 5f with high IC50 value 6 nM (against ovarian cancer, KF-28 cell line). Compound 5f-induced appreciated apoptotic cell death was measured as 82.76% associated with cell cycle arrest at the G1 phase. The apoptotic pathways activated in KF-28 cells treated with 5a, 5b, and 5f were further investigated. The upregulation of some pro-apoptotic genes, bax and puma, and the downregulation of some anti-apoptotic genes including the Bcl-2 gene were observed, indicating activation of the mitochondrial-dependent apoptosis. Together with the molecular docking studies of compounds 5a and 5b, our data revealed potential Pim-1 kinase inhibition through their high binding affinities indicated by inhibition of phosphorylated C-myc as a downstream target for Pim-1 kinase. Our study introduces a set of bis-thiazoles with potent anti-cancer activities, in vitro.

Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic / prognostic potential.

Investigating the etiological causes of acute myeloid leukemia (AML) at the molecular level should help in identifying targets and strategies that would increase the efficacy of the current management regimens. Some genes may act as molecular diagnostics, of these ASXL1 and PHF6 are involved in regulation of gene expression, and BAX , and ARC, are pro- and anti-apoptotic molecules, respectively. In this study, peripheral blood samples were collected from 54 recently diagnosed AML patients in addition to 20 healthy individuals (the control group). Cellular RNA was extracted from all the samples and were subjected to quantitative analysis of the transcript levels of the four selected markers. Our data showed a significant elevation in the expression levels of PHF6 and ARC in AML patients, when compared to the controls (77.8% and 83.3%, respectively). On the other hand, ASXL1 and BAX exhibited increase, to a lesser extent, in the expression levels of the AML patients (52% and 55.6%, respectively). Our study also showed that the expression levels of ARC and PHF6 exhibited a concomitant increase and this could be correlated with poor prognosis of the cases. Thus, we can suggest these markers as reliable prognostic markers for prediction of AML outcomes.

High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents.

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a-j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a-e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a-j exhibited promising cytotoxicity's against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

Inhibitory activities of indolizine derivatives: a patent review.

INTRODUCTION: Indolizines are structural isomers with indoles. Although several indole-based commercial drugs are available in the market, none of the indolizine-based drugs are available up-to-date. Natural and synthetic indolizines have a wide-range of pharmaceutical importance such as antitumor, antimycobacterial, antagonist, and antiproliferative activities. This prompted us to search and collect all possible data about the pharmacological importance of indolizine to open an avenue to the researchers in exploring more medicinal applications of such biologically important compounds. AREAS COVERED: The current review article covers the advancements in the biological and pharmacological activities of indolizine-based compounds during the last decade. The covered areas of this work involved anticancer, anti-HIV-1, anti-inflammatory, antimicrobial, anti-tubercular, larvicidal, anti-schizophrenia, CRTh2 antagonist's activities in addition to enzymatic inhibitory activity. EXPERT OPINION: The discovery of indolizine drugs will be a major breakthrough as compared with their widely available drug-containing indole isosteres. Major work collected here was focused on anticancer, anti-tubercular, anti-inflammatory, and enzymatic inhibitory activities. The SAR study of the reported biologically active indolizines is summarized throughout the review whenever highlighted to the rationale the behavior of inhibitory action. Several indolizines with certain functions provided great enhancement in the therapeutic activities comparing with reference drugs.

An update on benzofuran inhibitors: a patent review.

Introduction: Benzofuran is a fundamental unit in numerous bioactive heterocycles. They have attracted chemists and medical researchers due to their broad range of biological activity, where some of them possess unique anticancer, antitubercular, antidiabetic, anti-Alzheimer and anti-inflammatory properties. The benzofuran nucleus is present in a huge number of bioactive natural and synthetic compounds. Benzofuran derivatives have potent applications in pharmaceuticals, agriculture, and polymers. The recent developments considering the biological activities of benzofuran compounds are reported. They have a vital role as pronounced inhibitors against a number of diseases, viruses, fungus, microbes, and enzymes. Areas covered: This review covers the recent developments of biological activities of benzofurans during the period 2014-2019. The covered areas here comprised antimicrobial, anti-inflammatory, antitumor, antitubercular, antidiabetic, anti-Alzheimer, antioxidant, antiviral, vasorelaxant, anti-osteoporotic and enzyme inhibitory activities. Expert opinion: In addition to the already commercialized 34 benzofurans-based drugs in the market, this chapter outlines several potent benzofuran derivatives that may be useful as potential pro-drugs. It is also focused on providing details of SAR and the effect of certain functional groups on the activity of the benzofuran compounds. The presence of -OH, -OMe, sulfonamide, or halogen contributed greatly to increasing the therapeutic activities comparing with reference drugs.

Biological evaluation of benzosuberones.

INTRODUCTION: Several natural products containing benzosuberone moiety are clinically reported as anti-tumor agents. Furthermore, several synthetic benzosuberones cited in this review exhibited wide range of theraputic activities such as bacteriostatic, anti-inflammatory, antidepressants and anti-tumor activities. Our recent review provides an overview of the different methods to synthesize the benzosuberones and their extensive biological activities. AREAS COVERED: Thirty-two patents among 130 references are cited in this review that covered the recent inhibitory activities of the benzosuberone scaffolds and their broad area of biological applications up to the first quarter of 2017. The areas covered included anti-inflammatory, antimicrobial, antitumor, selective estrogen receptor, anti-obesity, beta-amyloid production, enzymes and HCV inhibitors in addition to anti-Alzheimer and anti-tuberculosis activities as well as several receptors antagonists. EXPERT OPINION: It is important for medical and pharmaceutical researchers to prepare the first intensive review article concerning the highly biologically active benzosuberone derivatives where they are potent anti-inflammatory, immunosuppressive, antitumor activities and inhibitors of several enzymes. They are useful for treating abnormalities such as sleep disorders, eating disorders and reproductive disorders. Some of these compounds have potential as vascular disrupting agents to selectively target microvessels feeding tumors and some were potential leads for the development of promising therapeutic drugs.

Thiadiazole inhibitors: a patent review.

INTRODUCTION: Four isomeric structures of thiadiazole motifs have outstanding pharmacological inhibitory applications are reported in this review. Thiadiazole nucleus is present in several biologically active natural products and commercial drugs. Most of thiadiazoles reported herein are emphasized to have broad spectrum of medicinal activities. Areas covered: This review represents the recent inhibitory activities of thiadiazole isomeric scaffolds and their broad-spectrum biological applications published as full texts during 2010-2016 as well as the patents published during 2005-2016. The inhibition areas covered included anti-inflammatory, antimicrobial, antitumor, antioxidant, antitubercular, antiviral, antileishmanial, anticonvulsant, herbicidal and algicidal activities in addition to enzymes, human platelet aggregation and neuroprotective inhibitors. Expert opinion: This survey revealed very interesting data about the applications of thiadiazoles, where some synthetic or natural thiadiazole derivatives were components of drugs available in the market. Many thiadiazole derivatives can be considered as lead compounds for drug synthesis. The most inhibitory active 1,3,4-thiadiazole compounds are those incorporating secondary alkyl(aryl)amido- and/or benzylthio(mercapto) groups at positions 2 and 5. Several thiadiazole derivatives demonstrated higher antibacterial, antitumor and antiviral activities than the standard drugs. Some thiadiazole derivatives exhibited high selective enzymes inhibitory activities based on the electronic properties of the substituents at positions 2 or 5.

Synthesis of 2-phenylazonaphtho[1,8-ef][1,4]diazepines and 9-(3-arylhydrazono)pyrrolo[1,2-a]perimidines as antitumor agents.

Two series of naphtho[1,8-ef][1,4]diazepines and pyrrolo[1,2-a]perimidines were prepared starting from 1,8-diaminonaphthalene and hydrazonoyl chlorides. The structures of the products were determined on the basis of their spectral data and elemental analyses. The mechanism of formation of such products was also discussed. The prepared compounds were screened for their antitumor activity against three cell lines, namely, MCF-7, TK-10 and UACC-62, and some derivatives showed promising activity.

Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents.

N-(4-(Pyrazol-4-yl)thiazol-2-yl)-N'-phenylthiourea derivative 2 was synthesized and then treated with variety of hydrazonoyl chlorides under basic condition at reflux to afford the corresponding 2-(4-(pyrazol-4-yl)thiazol-2-ylimino)-1,3,4-thiadiazole derivatives 6, 10a-e and 17a-e. Reaction of 2 with ethyl chloroacetate and with 3-chloro-2,4-pentanedione gave the thiazolidin-4-one 22 and 1,3-thiazole 25 derivatives, respectively. Condensation of thiazolidin-4-one 22 with aldehydes gave their 5-arylidene derivatives 23a-f. Most of the synthesized compounds were tested for anticancer activity against human hepatocelluar carcinoma HepG2, human breast cancer MCF-7 and human lung cancer A549. Their SAR was studied and variously affected by the electronic factor of electron donating and withdrawing groups. Many of the tested compounds showed moderate to high anticancer activity.

Benzofuran derivatives: a patent review.

INTRODUCTION: Benzofuran moiety constitutes the core of several interesting pharmacologically active natural products. Benzofurans are among feasible potent active inhibitors against many diseases, viruses, microbes, fungus and enzymes. Several series of therapeutically important synthetic and naturally occurring benzofuran-containing compounds are reported in this chapter. AREAS COVERED: The current chapter focuses on the recent applications of benzofuran scaffolds and their wide range of biological activities during 1999 - 2012. The pharmacological areas covered included anti-inflammatory, antitumor, cytotoxic, antimicrobial, antitubercular, antioxidant, antiplasmodial, trypanocidal and insecticidal activities as well as enzyme inhibitory, HCV and HIV inhibitory activities. EXPERT OPINION: The results reported in the chapter indicate that some benzofuran derivatives may be useful as potent drugs. From the structure-activity relationship (SAR), the presence of certain functions like -OH, -OMe in the benzofuran derivatives contributed greatly in increasing the potency of their therapeutic activities when compared with standards. For example, presence of the -OH and -OMe have made some benzofuran compounds more potent HIV-RT inhibitory activity than the standard atevirdine, and more potent antitumor agent when compared with standards (fluorouracil, doxorubicin and cytarabine). In addition, the enzyme aromatase CYP19 inhibitory activity of benzofurans having -OH and -OMe were greater than that observed for the reference arimidex.

Microwave-assisted synthesis and in-vitro anti-tumor activity of 1,3,4-triaryl-5-N-arylpyrazole-carboxamides.

Regioselective 1,3-dipolar cycloaddition of nitrilimines with 5-arylidene-2-arylimino-4-thiazolidinones and with 2-(4-arylidene)thiazolo[3,2-a]benzimidazol-3(2H)-ones afforded the corresponding 1,3,4-triaryl-5-N-arylpyrazole-carboxamides and pyrazolylbenzimidazoles. All reactions were carried out under conventional thermal heating and/or microwave irradiation. Both the pyrazole-5-carboxamides and pyrazolylbenzimidazoles were examined for their in-vitro anti-tumor activities against two tumor cell lines, Hep-2 and colon CaCo-2. Most of the obtained compounds exhibited significant activity against CaCo-2 and Hep-2 cell lines.