Novel 3-(4,6-dimethoxybenzofuran-5-yl)-1-phenyl-1H-pyrazole-4-carboxaldehyde (3) and 3-chloro-3-(4,6-dimethoxybenzofuran-5-yl)propenal (4) were prepared via Vilsmeier–Haack reaction of 1-(4,6-dimethoxybenzofuran-5-yl)ethanone (1) and its hydrazone derivative 2. Reaction of compound 4 with some hydrazine derivatives, namely hydrazine hydrate, phenylhydrazine and benzylhydrazine hydrochloride led to the formation of pyrazole derivatives 5–8, respectively. On the other hand, reaction of compound 4 with thiourea, urea or guanidine gave the pyrimidine derivatives 9–11, respectively. Reaction of amino compound 11 with acetic anhydride, benzoyl chloride and benzenesulphonyl chloride yielded N-substituted pyrimidine derivatives 12–14, respectively. Reaction of diazonium salt of compound 11 with sodium azide afforded azidopyrimidine derivative 15, which upon reaction with ethyl acetoacetate gave 1,2,3-triazole derivative 16. Acid catalyzed reaction of 11 with p-nitrobenzaldehyde gave Schiff base 17, which cyclized upon reaction with thioglycolic acid or chloroacetyl chloride to give thiazolidin-4-one 18 and azetidin-2-one 19, respectively. The newly synthesized compounds were tested for their anti-inflammatory, analgesic and anticonvulsant activities. Depending on the obtained results, the newly synthesized compounds possess significant anti-inflammatory, analgesic and anticonvulsant activities

Synthesis and biological activity of some new 1-benzyl and 1-benzoyl-3-heterocyclic indole derivatives: Starting from 1-benzyl- (2a) and 1-benzoyl-3-bromoacetyl indoles (2b) new heterocyclic, 2-thioxoimidazolidine (4a, b), imidazolidine-2,4-dione (5a, b), pyrano(2,3-d)imida-zole (8a, band9a, b), 2-substituted quinoxaline (11a, b-17a, b) and triazolo(4,3-a)quinoxaline derivatives (18a, band19a, b) were synthesized and evaluated for their antimicrobial and anticancer activities. Antimicrobial activity screening performed with concentrations of 0.88, 0.44 and 0.22 μg mm^-2showed that 3-(1-substituted indol-3-yl)quinoxalin-2(1H)ones (11a, b) and 2-(4-methyl piperazin-1-yl)-3-(1-substituted indol-3-yl) quinoxalines (15a, b) were the most active of all the tested compounds towardsP. aeruginosa, B. cereusandS. aureuscompared to the reference drugs cefotaxime and piperacillin, while 2-chloro-3-(1-substituted indol-3-yl)quinoxalines (12a, b) were the most active against C.albicanscompared to the reference drug nystatin. On the other hand, 2-chloro-3-(1-benzyl indol-3-yl) quinoxaline12adisplay potent efficacy against ovarian cancer xenografts in nude mice with tumor growth suppression of 100.0 ± 0.3 %.

Quorum sensing (QS) is a bacterial cell-to-cell communication mechanism that plays an essential role in bacterial pathogenesis. QS governs bacterial behavior and controls biofilm formation, which in turn contributes to antibiotic resistance. Therefore, identifying and synthesizing novel compounds to overcome QS and inhibit biofilm formation are essential. Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications, including antibacterial, antifungal, anticoagulant, antioxidant, anticancer, and anti-inflammatory properties. Additionally, coumarins are capable of QS rewiring and biofilm formation inhibition, leading to higher susceptibility to antimicrobial agents and less antibiotic resistance. Therefore, in this review, we aim to provide an overview of QS and biofilm formation. This review also discusses the role of natural and synthesized coumarins in controlling QS, inhibiting biofilm formation, and inducing synergy in antibiotic–coumarin combinations. Hence, this review emphasizes the potential of coumarin compounds to act as antibacterial agents and demonstrates their ability to alleviate antibiotic resistance.

A series of 1-(N-methyl 2a–c and N-benzenesulphonyl-1H-indol-3-yl)-3-aryl-prop-2-ene-1-ones 3a–c were prepared and allowed to react with urea, thiourea or guanidine and gave the pyrimidine derivatives 4a–c to 9a–c. Base catalyzed reaction of 2a–c or 3a–c with ethyl acetoacetate gave cyclohexanone derivatives 10a–c and 11a–c, respectively. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives 12a–c and 13a–c, respectively. On the other hand, condensation of 2c or 3c with some hydrazine derivatives namely, hydrazine hydrate, acetyl hydrazine, phenyl hydrazine and benzyl hydrazine hydrochloride gave pyrazole derivatives 14a,b-17a,b, respectively. Moreover, reaction of 2c or 3c with hydroxyl amine hydrochloride gave isoxazole derivatives 18a,b. The newly synthesized compounds were tested for their antimicrobial activity and showed that, compounds 14a, 14b, 15a and 15b were found to be the most active ones of all the tested compounds toward Salmonella typhimurium (ATCC 14,028) compared to the reference drug chloramphenicol. Eighteen new compounds namely, pyrimidin-2(1H)-ones 4a–c and 5a–c, pyrimidin-2(1H)-thiones 6a–c and 7a–c and pyrimidin-2-amines 8a–c and 9a–c were tested for their in vitro cytotoxicity against human liver carcinoma (HEPG2), human breast cancer (MCF7) and human colon cancer (HCT-116) cell lines and showed that, compounds 4c, 5c, 6c, 8c and 9c were found to be the highly active compounds compared to the reference drug doxorubicin

The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC₅₀ values obtained were 5.7–21.3 and 5.8–37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC₅₀ values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h exhibited the highest cytotoxicity with IC₅₀ value of 19.2µg/mL relative to doxorubicin (IC₅₀ = 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.

Synthesis and potential biological activity of some novel 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles and 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles: Starting fromN-substituted indole-3-carboxaldehydes (1a-g) a series of new 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles (3a-gand4a-g) have been synthesizedviathe acid catalyzed condensation reaction of1a-gwith 3-amino-5-pyrazolone, followed by the reaction with arylidene malononitriles. A series of new 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles (7a-g) have been prepared eitherviathe base catalyzed condensation reaction of1a-gwith 3-amino-5-pyrazolone to give6a-g, followed by the reaction with malononitrile or by the reaction ofN-substituted-3-indolylidene malononitriles (5a-g) with 3-amino-5-pyrazolone. According to the obtained results, the newly synthesized compounds possess significant anti-inflammatory, analgesic and anticonvulsant activities. The anticonvulsant potency of certain tested compounds was more pronounced than both anti-inflammatory and analgesic activities. Moreover, most of the newly synthesized compounds possess potential antimicrobial activity againstEscherichia coliandPseudomonas aeruginosa.