This review gives an up-to-date overview of the different ways (routes) to the synthesis of coumarin (benzopyrone)-fused, five-membered aromatic heterocycles with one heteroatom, built on the pyrone ...moiety. Covering 1966 to 2020.
Mercapto (or sulfanyl)-coumarins are heterocycles of great interest in the development of valuable active structures in material and biological domains. They represent a highly exploitable class of ...compounds that open many possibilities for further chemical transformations. The present review aims to draw focus toward the synthetic applicability of various forms of mercapto-coumarins and their representations in pharmaceuticals and industries. This work covers the literature issued from 1970 to 2021.
An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component ...condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial acetic acid led to the formation of 2,6-bis(1
-indol-3-yl)-4-(substituted-phenyl)pyridine-5-carbonitriles. Additionally, 2,6-bis(1
-indol-3-yl)-4-(benzofuran) pyridine-5-carbonitriles were prepared via a one-pot four-component condensation of 3-cyanocarbomethylindole, various
-substituted-indole-3-aldehydes, 2-acetylbenzofuran, and ammonium acetate. The synthesized compounds were evaluated for their ability to inhibit biofilm formation against the Gram-positive bacterial reference strains
ATCC 6538 and the Gram-negative strain
ATCC 25922. Some of the new compounds showed a marked selectivity against the Gram-positive and Gram-negative strains. Remarkably, five compounds
,
,
,
and
demonstrated good antibiofilm formation against
and
. On the other hand, the release of reducing sugars and proteins from the treated bacterial strains over the untreated strains was considered to explain the disruption effect of the selected compound on the contact cells of
and
. Out of all studied compounds, the binding energies and binding mode of bis-indole derivatives
and
were theoretically the best thymidylate kinase, DNA gyrase B and DNA topoisomerase IV subunit B inhibitors.
Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram ...positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC
of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%).
Cdc25 phosphatases have been considered promising targets for anticancer development due to the correlation of their overexpression with a wide variety of cancers. In the last two decades, the ...interest in this subject has considerably increased and many publications have been launched concerning this issue. An overview is constructed based on data analysis of the results of the previous publications covering the years from 1992 to 2021. Thus, the main objective of the current review is to report the chemical structures of Cdc25s inhibitors and answer the question, how to design an inhibitor with better efficacy and lower toxicity?
For conjugating sulfa drug moieties with Schiff’s bases scaffold in the same build through an azo linker to take advantage of the bioactive feature of both motifs, we designed and synthesized a ...series of bioactive disperse dyes. The target disperse dyes, methyl 2-(
E
-2-hydroxy-5-((
E
)-(4-sulfa-derivative) diazenyl)benzylidene) hydrazine-1-carbodithioates
4a
–
e
have been synthesized via the acidic reaction of azo dyes
3a
–
e
with methyl hydrazine carbodithioate. Structures of the synthesized dyes were clarified based on their spectral and elemental analyses. The effectiveness of the dyes was initially tested as an antibacterial toward
Staphylococcus aureus
ATCC 6538-P and
Escherichia coli
ATCC 25933. Dyes that were proven to be effective against bacteria have been used as disperse dyes to print polyester fabrics. The color properties of the dyes and their fastness properties counting washing, perspiration, light, rubbing, and sublimation fastness were also examined. The printed polyester fabrics were evaluated for their antibacterial activity via colony-forming unit (CFU) technique. Fabric samples treated with
4c
,
4d
, and
4b
had promising anti-Gram-positive activities against
S. aureus.
Whereas
4c-
,
4d-
, and
4b
-treated fabrics exhibited moderate anti-Gram-negative activities against the test bacterium
E. coli
.
•Compounds formula, (E)−5-heptadecyl-4-(((1-benzyl-1H-indol-3-yl) methylene) amino)−4H-1,2,4-triazole-3-S-alkyl, where the alkyl group is ethan-1-ol (6d) or propane-1,2-diol)7d(showed antiviral ...activity against NRC-03-nhCoV with IC50 of 8.7 and 8.925 μM, respectively.•(E)−5-heptadecyl-4-(((1-methyl-1H-indol-3-yl)methylene)amino)−4H-1,2,4-triazole −3-thiol (5b) showed excellent MIC values against all test microbes with values of 19.53, 39.06, and 39.125 µg/mL against S. aureus, E. coli, and C. albicans, respectively.•Compound 5b exhibited release of reducing sugars and proteins with variable values on test microbes, which confirmed the effect of 5b on the bacterial cell well (biosynthesis of cell well peptidoglycan).•Compound 5b was confirmed to be able to disrupt outer and inner membranes and interact with membrane protein and intracellular targets by scanning electron microscopic study (SEM).•A molecular docking study of the potent compounds against the key viral and microbial protein targets has highlighted the antiviral and antimicrobial behavior of these compounds.
Two series of Schiff bases and Mannich bases derived from 5-heptadecyl-4H-1,2,4-triazole hybrids of indole moiety have been synthesized. First, the acid-catalyzed reaction of N-substituted-1H-indole-3-carboxaldehydes with the modified fatty acid, 4-amino-5-heptadecyl-4H-1,2,4-triazole-3-thiol, afforded 1,2,4-triazole Schiff bases 5a-d. Treatment of 5a-d with some halo-compounds gave S-alkyl-1,2,4-triazoles 6a-d to 9a-d. Additionally, the reaction of 5a-d with different secondary amine and paraformaldehyde afforded Mannich base products 10a-d to 13a-d. Basically, viral infections are often followed by bacterial infections that require antimicrobial treatment. The antiviral bioassay revealed that compounds 6d and 7d exhibited significant antiviral activity against NRC-03-nhCoV with IC50 equal 8.7 and 8.925 μM, respectively. Next, the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as yeast and fungi. Compound 5b exhibited effective antimicrobial activities against all microbial test strains. 5b revealed MIC values of 19.53 μg/mL against S. aureus, 39.063 μg/mL against E. coli, and 39.125 μg/mL against C. albicans. On top of that, the release of reducing sugars and proteins from the treated bacterial strains over the untreated bacterial strains was undertaken to describe the effect of compound 5b on the intact cells. Furthermore, scanning electron microscopy (SEM) has been applied to study the possible sterilization process of the antimicrobial compound 5b. The results indicated the possibility of destroying the cell membrane structure of microbes, resulting in incomplete microbial structures, and thus achieving inhibition. To putatively highlight the antiviral and antimicrobial activities of the potent compounds, they were subjected to molecular docking against the key viral and microbial protein targets.
Starting from N-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-g and 4a-g) have been ...synthesized via the acid catalyzed condensation reaction of 1a-g with 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 either via the base catalyzed condensation reaction of 1a-g with 3-amino-5-pyrazolone to give 6a-g, followed by the reaction with malononitrile or by the reaction of N-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 against Escherichia coli and Pseudomonas aeruginosa.
U radu se opisuje sinteza novih 3-N-supstituiranih indol-3-il)metilenamino6-amino-4-aril-pirano(2,3-c) pirazol-5-karbonitrila (3a-g i 4a-g) kiselo-kataliziranom kondenzacijom N-supstituiranih indol-3-karboksaldehida (1a-g) s 3-amino-5-pirazolonom iza koje slijedi reakcija s ariliden malononitrilom. Serija novih 3,6-diamino-4-(N-supstituiranih indol-3-il)pirano(2,3-c)pirazol-5-karbonitrila (7a-g) sintetizirana je reakcijom malononitrila s produktima 6a-g, koji su pripravljeni bazno-kataliziranom kondenzacijom 1a-g s 3-amino-5-pirazolonom. Neki spojevi iz serije 7a-g dobiveni su reakcijom N-supstituiranih 3-indolidin malononitrila (5a-g) s 3-amino-5-pirazolonom. Novosintetizirani spojevi imaju značajno protuupalno, analgetsko i antikonvulzivno djelovanje. Antikonvulzivno djelovanje pojedinih testiranih spojeva bilo je jače izraženo nego protuupalno i analgetsko djelovanje. Većina ispitivanih spojeva pokazuje antimikrobno djelovanje na Escherichia coli i Pseudomonas aeruginosa.
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.
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, b and 9a, b), ...2-substituted quinoxaline (11a, b-17a, b) and triazolo(4,3-a)quinoxaline derivatives (18a, b and 19a, 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-2 showed 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 towards P. aeruginosa, B. cereus and S. aureus compared 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. albicans compared to the reference drug nystatin. On the other hand, 2-chloro-3-(1-benzyl indol-3-yl) quinoxaline 12a display potent efficacy against ovarian cancer xenografts in nude mice with tumor growth suppression of 100.0 ± 0.3 %.
U radu je opisana sinteza, antimikrobno i antitumorsko djelovanje heterocikličkih derivata indola. Polazeći iz 1-benzil- i 1-benzoil-3-bromacetil indola (2a i 2b) sintetizirani su novi heterociklički spojevi 2-tioksoimidazolidini (4a, b), imidazolidin-2,4-dioni (5a, b), pirano(2,3-d)imidazoli (8a, b i 9a, b), 2-supstituirani kinoksalini (11a, b-17a, b) i triazolo(4,3-a)kinoksalini (18a, b i 19a, b). Sintetizirani spojevi testirani su na antimikrobno i antitumorsko djelovanje. Ispitivanje antimikrobnog djelovanja provedeno je s koncentracijama otopina 0,88, 0,44 i 0,22 μg mm-2 i usporedeno s referentnim lijekovima cefotaksimom i piperacilinom. Rezultati pokazuju da su 3-(1-supstituirani indol-3-il)kinoksalin-2(1H)oni (11a, b) i 2-(4-metil piperazin-1-il)-3-(1-supstituirani indol-3-il) kinoksalini (15a, b) najaktivniji spojevi na sojeve P. aeruginosa, B. cereus i S. aureus, dok su 2-klor-3-(1-supstituirani indol-3-il)kinoksalini (12a, b) najaktivniji na C. albicans (usporedba s nista-tinom). Osim toga, 2-klor-3-(1-benzil indol-3-il) kinoksalin (12a) pokazuje veliku učinkovitost na tumore ovarija miševa (supresija rast a tumora 100 ± 0,3%).
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