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.

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.

Human ex-vivo oral tissue imaging using spectral domain polarization sensitive optical coherence tomography.

We report the use of spectral domain polarization sensitive optical coherence tomography for ex-vivo imaging of human oral mandibular tissue samples. Our results show that compared to the changes observed in the epithelium thickness and the decay constant of A-scan intensity profile, a much larger degree of change was observed in the phase retardation for tissue sites progressing from normal to the malignant state. These results suggest that monitoring of tissue retardance can help in better differentiation of normal and cancerous oral tissue sites.