1,3,5-Triazine: Recent Development in Synthesis of its Analogs and Biological Profile.

Triazine is an important pharmacophore in the field of research for the development of novel medications due to its presence in numerous powerful physiologically active compounds with significant medical potential, such as anti-tumor, anti-viral, anti-inflammatory, anti-microbial, anti- HIV, anti-leishmanial and others. The easy availability of triazine, high reactivity, simple synthesis of their analog, and their notable broad range of biological activities have garnered chemist interest in designing s-triazine-based drugs. The interest of medicinal chemists has been sparked by the structure-activity relationship of these biologically active entities, leading to the discovery of several promising lead molecules. Its importance for medicinal chemistry research is demonstrated by the remarkable progress made with triazine derivatives in treating a variety of disorders in a very short period. Authors have collated and reviewed the medicinal potential of s-triazine analogous to afford medicinal chemists with a thorough and target-oriented overview of triazine-derived compounds. We hope the present compilation will help people from the industry and research working in the medicinal chemistry area.

Synthetic and pharmacological developments in the hybrid s-triazine moiety: A review.

This article summarizes the most recent advancements in the synthetic and pharmacological approaches along with the structure activity relationship towards the s-triazine and its derivatives. Much attention has been given to s-triazine core due to its facile synthesis, interesting pharmacology, high reactivity, and binding characteristics towards various enzymes. An array of biological applications has been demonstrated by s-triazines including antimalarial, anti-HIV, anti-viral, antimicrobial, anti-tuberculosis to name a few. In the present investigation s-triazine based molecular structures have been assembled in respect to their synthesis and medicinal properties. Further, the competence of s-triazine has been correlated and compared with the other heterocyclic moieties to substantiates-triazine a privileged scaffold. From the literature it is revealed that nucleophilic substitution at 2, 4, and 6 positions is significant for various biological applications. This article would help in assisting the chemists in designing novel molecular entities with high medicinal value.

Development of novel bosentan analogues as endothelin receptor antagonists for pulmonary arterial hypertension.

Since decades, bosentan has been in use for the treatment of pulmonary arterial hypertension (PAH). However, chronic exposure to bosentan leads to the development of resistance, tolerance, and serious adverse effects that have restricted its usage in clinical practices. To surmount these limitations, some new bosentan derivatives have been synthesized and evaluated for their therapeutic efficacy in PAH. Molecular docking analyses of all the synthesized derivatives were carried out using the endothelin (ET) receptor. In addition, the inhibitory ability of synthesized derivatives was determined in in vitro assay employing an ET-1 human ELISA kit. Among the synthesized derivatives, three derivatives namely 17d, 16j, and 16h with higher docking scores and lower IC50 values were selected for determination of the magnitude of the binding force between the derivative and ET receptor using molecular dynamics (MD) simulations study. Further, these derivatives were subjected to in vivo studies using monocrotaline (MCT) induced PAH in rat model. Results of in vivo studies inferred that the derivatives exhibit impressive ability to reduce PAH. Besides, its protective role was also evidenced in hemodynamic and right ventricular hypertrophy analyses, histological analysis, cardiac biomarkers, hypoxia-inducible factor 1 alpha (HIF1α) levels, and biochemical studies. Furthermore, gene quantification by quantitative RT-PCR and Western blot analysis was also performed to examine its effect on the expression of key proteins in PAH. Notably, amongst three, derivative 16h exhibited the most encouraging results in molecular docking analysis, in vitro, in vivo, histopathological, biochemical, protein expression, and MD studies. Besides, derivative 16h also showed impressive pharmacokinetic features in ADMET analysis. In conclusion, derivative 16 h could act as a reliable ET receptor antagonist and requires further exploration to attain its therapeutic utility in PAH management.

Comprehensive Update on Synthetic Aspects of Bosentan Derivatives.

Bosentan and its analogues were first reported as endothelin (ET) receptor antagonists in US patent No. 5, 292,740 in 1994. Bosentan synthesis has been reported by employing different methods from the reaction between (4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine and 4- (tert-butyl) benzenesulfonamide and 4-(tert-butyl)-N-(6-chloro-5-(2-methoxyphenoxy)-[2,2'- bipyrimidin]-4-yl) benzenesulfonamide in the form of different salts like potassium salt, ammonium salt, sodium salt, and free, on its reaction with ethylene glycol. Several changes have been observed in the chemistry of the involved intermediate synthesis, particularly coupling chemistry, to produce bosentan derivatives with high purity and yield.

Synthesis and Theoretical Studies of Biologically Active Thieno Nucleus Incorporated Tri and Tetracyclic Nitrogen Containing Heterocyclics Scaffolds via Suzuki Cross-Coupling Reaction.

A new series of thieno nucleus embellished trinuclear (19, 20) and tetranuclear (21-24) nitrogen heteroaryl have been synthesized by the Suzuki cross-coupling reaction using bis(triphenylphosphine)palladium(II) dichloride. All the synthesized compounds were characterized by IR, 1 H-NMR, 13 CNMR and Mass spectral properties. In vitro antibacterial studies of the synthesized compound were conducted using broth microdilution assay employing Gram-positive and Gram-negative strains and half-maximal inhibitory concentration (IC50 ) was determined. The result showed that compound 20 possess best antibacterial activity against S. aureus and E. coli with IC50 values of 60 µg mL-1 and 90 µg mL-1 . Further to determine the mode of antibacterial action, compounds 20 and 21 were examined for in vitro bacterial dehydrogenase inhibitory assay. To understand the binding affinity of the synthesized compounds, the docking study was performed in the bacterial dehydrogenase enzyme by AutoDock Vina software and structure was confirmed by Discovery Studio Visualizer. All the synthesized compounds were docked in a good manner within the active sites of the bacterial dehydrogenase enzyme and exhibited good binding energies.

A comprehensive update on the structure and synthesis of potential drug targets for combating the coronavirus pandemic caused by SARS-CoV-2.

The outbreak of the coronavirus pandemic COVID-19 created by its severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variant, known for producing a very severe acute respiratory syndrome, has created an unprecedented situation by its continual assault around the world. The crisis caused by the SARS-CoV-2 variant has been a global challenge, calling to mitigate this unprecedented pandemic that has engulfed the whole world. Since the outbreak and spread of COVID-19, many researchers globally have been grappling to find new clinically trialed active drugs with anti-COVID-19 activity, from antimalarial drugs to JAK inhibitors, antiviral drugs, immune suppressants, and so forth. This article presents a brief discussion on the activity and synthesis of some active molecules such as favipiravir, hydroxychloroquine, pirfenidone, remdesivir, lopinavir, camostat, chloroquine, baricitinib, molnupiravir, and so forth, which are under trial.

Synthetic and Biological Attributes of Pyrimidine Derivatives: A Recent Update.

Nitrogen-containing heterocycles attract the attention of chemists due to their multifarious activities. Amongst all, pyrimidine plays a central role and exhibits a broad spectrum of biological activities. Literature is replete with various aspects of synthetic development in the chemistry of pyrimidine for a wide array of applications. It aroused our interest to compile various novel and efficient synthetic approaches towards the synthesis of pyrimidine and its derivatives. Pyrimidine derivatives are broadly useful as therapeutic agents, owing to their high degree of structural diversity. They have been recorded to possess a diverse range of therapeutic activities viz. anticancer, anti-inflammatory, anti-HIV etc.

Medicinal and Biological Significance of Phenoxazine Derivatives.

Since 1887, phenoxazine derivatives have attracted the attention of chemists due to their versatile utility, industrially and pharmacologically. Literature is found abundant with various pharmacological activities of phenoxazine derivatives like antitumor, anticancer, antifungal, antibacterial, anti-inflammatory, anti-diabetic, anti-viral, anti-malarial, anti-depressant, analgesic and many other drug resistance reversal activities. This review covers a detailed overview of the pharmacological application of phenoxazine nucleus, its chemistry and reactivity, and also illustrating the incorporation of different groups at different positions enhancing its biological application, besides some synthetic procedures.

A facile one pot synthesis of novel pyrimidine derivatives of 1,5-benzodiazepines via domino reaction and their antibacterial evaluation.

A new series of pyrimidine (8, 14, 18 and 23) embellished analogues of 1,5-benzodiazepines were synthesized by the one-pot domino approach using the catalyst DABCO (1,4-diazabicyclo[2.2.2]octane). For each compound synthesized, anti-microbial efficacy was determined using broth microdilution assay and half maximal inhibitory concentration (IC50). Furthermore, FESEM (Field emission scanning electron microscope) studies were also carried out to observe the effect of the structure of test compounds on the morphology of both Gram-positive (S. aureus) and Gram-negative (E. coli) cell walls. The leakage of nucleotides and their integral components from compromised bacterial cells was assessed by plotting the optical density (OD) with respect to time of exposure at 320 nm. Anti-bacterial studies revealed that compound 23 was most active against targeted bacterial species. Results of the antibacterial study indicated that all the test compounds possess significant antibacterial potential against targeted bacterial strains. Amongst all, in the FE-SEM study, compound 23 caused marked alteration in bacterial cell morphology and resulted in maximum leakage of cell nucleotides in bacterial strains as compared to controls. Further efforts are required to establish their efficacy as antibacterial agents in clinical management.

Application of Palladium-Catalyzed Cross-Coupling Reactions in Organic Synthesis.

Palladium-catalyzed cross-coupling reactions have gained a continuously growing interest of synthetic organic chemists. The present review gives a brief account of applications of the palladium-catalyzed cross-coupling reactions in comprehensive synthesis, viz., the Heck, Stille, Suzuki-Miyaura, Negishi, Sonogashira, Buchwald-Hartwig, Ullmann and the Oxidative, decarboxylative cross-coupling reactions, with particular emphasis on the synthesis of heterocyclic compounds.

The Synthetic and Biological Attributes of Pyrazole Derivatives: A Review.

Pyrazole nucleus is a unique structural scaffold which acts as an interesting template for combinatorial as well as medicinal chemistry. This review presents a detailed overview on the synthesis, QSAR and pharmacological applications of pyrazole. In addition, it covers most recent reports on structural modifications on pyrazole illustrating vital structural activity relationship.

Gastroprotective activity of reconstituted red fruit pulp concentrate of Citrullus lanatus in rats.

AIM: This study was carried out to evaluate the gastroprotective potential of the aqueous fruit pulp concentrate of Citrullus lanatus citroides (CLC) on pyloric ligation and indomethacin-induced ulcer in Wistar albino rats. MATERIALS AND METHODS: In indomethacin-induced ulcer model, CLC was administered in the doses of 250 mg/kg, 500 mg/kg and 1000 mg/kg body weight orally, tds for 5 days. The antiulcer activity was determined via observing reduction in ulcer index whereas in the pyloric ligation model, the gastroprotective effect of CLC was assessed from the alteration in volume of gastric juice, pH, free and total acidity, protein concentration in gastric juice. Further lipid peroxide (LPO), and activities of enzymic antioxidants such as superoxide dismutase (SOD) and catalase (CAT) was also determined along with the levels of hexose, hexosamine, sialic acid, fucose in gastric mucosa. RESULTS: In both models, treatment with CLC caused a significant reduction in lesion index when compared to vehicle treated group, providing evidence for antiulcer capacity. In pyloric ligation model, pretreatment with CLC resulted in significant increase in pH, enzymic antioxidants, that is, SOD, CAT, with a significant decrease in volume of gastric juice, free and total acidity, protein concentration, acid output, and LPO levels respectively. The presence of the flavonoids and polyphenols may be responsible for the gastroprotective effect of CLC. CONCLUSIONS: The aqueous fruit pulp concentrate of CLC showed significant gastroprotective potential against pyloric ligation and indomethacin-induced ulceration in rats.