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.

Recent Methods for the Synthesis of Quinoxaline Derivatives and their Biological Activities.

Quinoxaline derivatives have been incorporated into numerous marketed drugs used for the treatment of various diseases. Examples include glecaprevir (Mavyret), voxilaprevir (Vosevi), Balversa (L01EX16) (erdafitinib), carbadox, XK469R (NSC698215), and becampanel (AMP397). These quinoxaline derivatives exhibit a diverse range of pharmacological activities, including antibacterial, antitubercular, antiviral, anti-HIV, anti-inflammatory, antifungal, anticancer, antiproliferative, antitumor, kinase inhibition, antimicrobial, antioxidant, and analgesic effects. Recognizing the significance of these bioactive quinoxaline derivatives, researchers have dedicated their efforts to developing various synthetic methods for their production. This review aimed to compile the most recent findings on the synthesis and biological properties of quinoxaline derivatives from 2015 to 2023.

The most recent compilation of reactions of enaminone derivatives with various amine derivatives to generate biologically active compounds.

Heterocyclic derivatives serve as the fundamental components of both natural and synthetic drugs. Enaminones play a crucial role as foundational units in the synthesis of numerous bioactive heterocyclic compounds, including pyrazoles, pyridines, oxazoles, isoxazoles, as well as fused heterocyclic structures like indoles, carbazoles, quinolines, acridines, and phenanthridines. These diverse heterocyclic rings are well-known for their various therapeutic activities, encompassing anticancer, anti-inflammatory, antimicrobial, antidepressant, and antiviral properties. By reacting with nitrogen-based nucleophiles, enaminones can generate bioactive azoles, azines, and their fused systems. This comprehensive review article focuses on the recent advancements in enaminone reactions with (a) nitrogen-based nucleophiles, such as aliphatic amines, derivatives of aniline, heterocyclic amines, hydroxylamine, hydrazine derivatives, guanidine derivatives, urea, and thiourea derivatives, and (b) nitrogen-based electrophiles, such as diazonium salts. These reactions have led to the synthesis of a wide range of bioactive fused heterocyclic compounds from 2010 to the end of 2022.

Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors.

With the aim of developing cyclin-dependent kinase 2 (CDK2) inhibitors with strong antibreast cancer efficacy, new tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives were synthesized. The newly synthesized tri- and tetracyclic derivatives were achieved from the reaction of 4-(4-morpholin-4-yl-phenyl)-1,3,4,5,6,7-hexahydro-benzo[6,7]cyclohepta[1,2-d]pyrimidine-2-thione (5) with α-haloketone derivatives as hydrazonyl chlorides, phenacyl bromide derivatives, chloroacetone, and ethyl substituted acetate derivatives. The MCF-7 and MDA-MB-231 breast cancer cell lines were utilized to examine the anticancer properties. Compounds 5 and 8 were shown to be the most effective, with half-maximal inhibitory concentration (IC50 ) values between 5.73 and 9.11 µM, which are on the level with doxorubicin. Mechanistic studies showed that 5 and 8 caused tumor cell death by inducing apoptosis and they also produced cancer arrest in the S phase of the cell cycle. In addition, compounds 5 and 8 showed strong anti-CDK2 action (IC50 = 0.112 and 0.18 µM, respectively) comparable to roscovitine (IC50 = 0.127 µM). Moreover, the docking result demonstrated that derivatives 5 and 8 fit into the CDK2 active site in the proper orientation.

The patent review of the biological activity of tropane containing compounds.

INTRODUCTION: Tropane-derived medications have historically played a substantial role in pharmacotherapy. Both natural and synthetic derivatives of tropane find application in addressing diverse medical conditions. Prominent examples of tropane-based drugs include hyoscine butylbromide, recognized for its antispasmodic properties, atropine, employed as a mydriatic, maraviroc, known for its antiviral effects. trospium chloride, utilized as a spasmolytic for overactive bladder, and ipratropium, a bronchodilator. AREAS COVERED: We compiled patents pertaining to the biological activity of substances containing tropane up to the year 2023 and categorized them according to the specific type of biological activity they exhibit. ScienceFinder, ScienceDirect, and Patent Guru were used to search for scientific articles and patent literature up to 2023. EXPERT OPINION: Pharmaceutical researchers in academic and industrial settings have shown considerable interest in tropane derivatives. Despite this, there remains a substantial amount of work to be undertaken. A focused approach is warranted for the exploration and advancement of both natural and synthetic bioactive molecules containing tropane, facilitated through collaborative efforts between academia and industry. Leveraging contemporary techniques and technologies in medicinal and synthetic chemistry, including high throughput screening, drug repurposing,and biotechnological engineering, holds the potential to unveil novel possibilities and accelerate the drug discovery process for innovative tropane-based pharmaceuticals.

Synthesis of new Spiropyrazole derivatives under microwaves irradiation and docking study for inhibition the microbes and COVID-19.

Synthesis of a new series of spiropyrazole derivatives using microwaves irradiation with high yield in minutes was achieved through a cycloaddition reaction of nitrile imines and arylidenes of 5-bromo-indan-1-one. The structure of the new spiropyrazoles was assured based on their available spectral analyses and the comparison of the extracted data with the literature reports. Molecular docking simulations of all new synthesized spiropyrazole derivatives into leucyl-tRNA synthetase editing domain of Candida albicans (Pdb: 2WFC) indicated that about seven spiropyrazole derivatives can fit deeply in the active site via the formation of stable complexes. In addition, the docking study was utilized to tested the ability of these spiropyrazoles to inhibit COVID-19 through the interaction with COVID-19 main protease (Pdb: 6LU7). The results were surprising which revealed high docking score ranging from -7.764 to -5.9464 kcal/mol. Moreover, the nitrogen atom of pyrazole, Br atom and the C=O group of indanone are essential parts in the binding mode of almost the active derivatives. The results of the docking study are a glimmer of hope to complete the study on these compounds and examine them in the laboratory to ensure their effectiveness as antimicrobials and antiviral, especially Covid-19. Moreover, pharmacokinetics and physicochemical properties were studied.

Novel anti-tubercular and antibacterial based benzosuberone-thiazole moieties: Synthesis, molecular docking analysis, DNA gyrase supercoiling and ATPase activity.

Herein, molecular hybridization strategy was utilized in the design of new benzosuberone-thiazole derivatives. The structures of the synthesized hybrids were determined on the basis of elemental and spectral analyses. These compounds were evaluated for their antibacterial activities against five bronchitis causing bacteria in addition to their anti-tubercular activities. Most compounds revealed promising activities. Amongst active compounds, benzosuberone-dithiazole derivatives 22a and 28 with MIC value = 1.95 µg/ml against H. influenza, M. pneumonia, and B. pertussis displayed four times the activity of ciprofloxacin (MIC = 7.81 µg/ml) against H. influenza, twice the activity of ciprofloxacin (MIC = 3.9 µg/ml) against M. pneumonia and were equipotent to ciprofloxacin against B. pertussis (MIC = 1.95 µg/ml). Additionally, benzosuberone-dithiazole derivatives 22a and 27 were the most promising anti-tubercular among the tested compounds with MIC values of 0.12 and 0.24 µg/ml, respectively against sensitive M. tuberculosis in addition to high activity against resistant strain of M. tuberculosis (MIC = 0.98 and 1.95 µg/ml, respectively) compared to isoniazid (MIC = 0.12 µg/ml against sensitive M. tuberculosis and no activity against resistant M. tuberculosis). Cytotoxicity study of the active dithiazole derivatives 22a, 27 and 28 against normal human lung cells (WI-38) indicated their high safety profile as showed from their high IC50 values (IC50 = 107, 74.8, and 117 µM, respectively). Furthermore, DNA gyrase supercoiling and ATPase activity assays showed that 22a, 27 and 28 have the potential to inhibit DNA gyrase at low micromolar levels (IC50 = 3.29-15.64 µM). Molecular docking analysis was also carried out to understand the binding profiles of the synthesized compounds into the ATPase binding sites of bacterial and mycobacterial DNA gyraseB.

Discovery of thiazole-based-chalcones and 4-hetarylthiazoles as potent anticancer agents: Synthesis, docking study and anticancer activity.

The crucial need for novel antitumor agents with high selectivity toward cancer cells has promoted us to synthesize new series of thiazole-based chalcones and 4-hetarylthiazoles (rigid chalcones). The synthesis of thiazolyl chalcones and 4-hetarylthiazoles and the assertion of their structure are described. Their anti-proliferative activity was estimated against three human cancer cell lines; HepG-2, A549 and MCF-7. 3-(4-Methoxyphenyl)-1-(5-methyl-2-(methylamino)thiazol-4-yl)prop-2-en-1-one (chalcone derivative 3a) showed significant and broad antitumor activity that was more potent than Doxorubicin. In addition, compounds 3d, 3e and 7a displayed potent activity compared to Doxorubicin. Additionally, these compounds were less toxic on normal lung cells WI-38 with high selectivity index. Further study on 3a regarding its effect on the normal cell cycle profile in A549 cells demonstrated cell cycle arrest at the G2/M phase together with rise in the percentage of the apoptotic pre-G1 cells. CDK1/CDK2/CDK4 inhibition assays were carried out on 3a, 3d, 3e and 7a and the results revealed non selective inhibition on the tested CDKs with IC50 values of 0.78-1.97 µM. Moreover, docking study predicted that 3a, 3d, 3e and 7a can fit in the ATP binding site of CDK1 enzyme. The apoptosis induction potential of 3a, 3d, 3e and 7a was also estimated against some apoptosis markers. Interestingly, they elevated the level of Bax by 6.36-10.12 folds and reduced the expression of Bcl-2 by 1.94-4.12 folds compared to the control. Furthermore, they increased both active caspase-3 and p53 levels by 8.76-10.56 and 6.85-10.36 folds, respectively higher than the control which indicates their potential to induce apoptosis.

Anti-inflammatory, Analgesic and Anti-ulcerogenic Activities of Novel bis-thiadiazoles, bis-thiazoles and bis-formazanes.

BACKGROUND: Indane-1,3-dione, thiazole, bis-thiazole and thiadiazoles rings are very interested moieties in anti-inflammatory and analgesic drugs. OBJECTIVE: The goal of this work is to synthesize new derivatives of bis-thiazoles and bis-1,3,4- thiadiazoles for the investigation of their anti-inflammatory, anti-ulcerogenic and analgesic activities. METHODS: 1,1'-(1,2-phenylene)bis(3-phenylthiourea) (1) reacts with a number of N-aryl arenecarbohydrazonoyl chlorides 2 to give a series of new bis-1,3,4-thiadiazoles 4. Also, reaction of bisthiosemicarbazone of 1,3-indanedione 6 with another type of hydrazonoyl halides namely, N-aryl-2- oxapropanehydrazonoyl chlorides 7 and ethyl-(N-arylhydrazono)chloroacetate 8 in dioxane under reflux in the presence of triethylamine give the respective bis-thiazole derivatives 9 and 10, respectively. The products 9 and 10 can exist in five and seven tautomeric forms for each one. Their actual tautomeric forms were deduced based on electronic absorption data (UV / Vis spectra). Moreover, a series of novel bis-formazans 12 and 13 have been synthesized by reaction of 1,3-dihydrazono-2,3- dihydro-1H-indene (11) with both hydrazonoyl chlorides 7 and 8. RESULTS: The structure of all the novel products was deduced by elemental analysis and spectral data. In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, anti-ulcerogenic and analgesic agents. CONCLUSION: In this context, we synthesize new derivatives of bis-thiazoles and bis-1,3,4-thiadiazoles as anti-inflammatory, anti-ulcerogenic and analgesic agents.

New and efficient approach for synthesis of novel bioactive [1,3,4]thiadiazoles incorporated with 1,3-thiazole moiety.

A series of novel 1,3,4-thiadiazoles incorporated with thiazole moiety was synthesized by reaction of 5-acetyl-2-benzoylimino-3-phenyl-1,3,4-thiadiazole thiosemicarbazone 2 with each of N-phenyl 2-oxo-propanehydrazonoyl chloride 3 and ethyl (N-aryl-hydrazono) chloroacetate 5 in dioxane in basic medium. Also, another series of 1,3,4-thiadiazole incorporated with thiazole moiety was prepared by reaction of 5-acetyl-2-benzoylimino-3-phenyl-1,3,4-thiadiazole thiocarbohydrazone with each of hydrazonoyl chlorides 3, 5 and 18 under the same reaction conditions. The mechanisms of the studied reactions were discussed and the assigned structure for each of the new products was identified via elemental and spectral data and by alternative method whenever possible. Moreover, the antimicrobial activity for some selected products was screened, and the results obtained exploring the high potency of some of the tested compounds compared with the employed standard bactericides and fungicide.

Efficient synthesis and antimicrobial evaluation of some Mannich bases from 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones.

BACKGROUND: Thiazolidinone, has been employed in the preparation of different important drugs required for treatment of inflammations, bacterial infections, and hypertension. Mannich bases have been shown to exhibit diverse biological activities, such as antibacterial, and antifungal activities. Spiroheterocycles including thiazolidine moiety have antimicrobial activity. RESULTS: In this study, a novel, rapid, and efficient protocol is developed for the synthesis of various 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones using sodium dodecylbenzene sulfonate (DBSNa) as an inexpensive and readily available reagent in acetic acid at room temperature. High yields, easy work-up, and short reaction times are advantages of this procedure. The synthesized arylidines were undergone Mannich reaction with formaldehyde and secondary amines in absolute ethanol at room temperature to afford the corresponding N-Mannich bases. All prepared Mannich bases were evaluated for their antimicrobial activity. CONCLUSIONS: Good activity was noted for Mannich bases from 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones, with some members recorded higher antimicrobial activity. Graphical abstractSynthesis of Mannich bases of 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones.