Synthesis, and Molecular Structure Investigations of a New s-Triazine Derivatives Incorporating Pyrazole/Piperidine/Aniline Moieties

In this work, we synthesized two new s-triazine incorporates pyrazole/piperidine/aniline moieties. Molecular structure investigations in the light of X-ray crystallography combined with Hirshfeld and DFT calculations were presented. Intermolecular interactions controlling the molecular packing of 4-(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5a and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5b were analyzed using Hirshfeld calculations. The most dominant interactions are the H...H, N...H and H...C contacts in both compounds. The N...H and H...C interactions in 5a and the N...H, Br...H and H...H interactions in 5b are the most important. In addition, DFT calculations were used to compute the molecular structures of 5a and 5b; then, their electronic properties, as well as the 1H- and 13C-NMR spectra, were predicted. Both compounds are polar where 5a (1.018 Debye) has lower dipole moment than 5b (4.249 Debye). The NMR chemical shifts were calculated and very good correlations between the calculated and experimental data were obtained (R2 = 0.938–0.997).

Pharmacological Evaluation of Novel 1,2,4-triazine Derivatives Containing Thiazole Ring Against Hepatocellular Carcinoma

Background: New 6-hydroxy-5-(p-hydroxybenzylidene)-3-phenyl-2-[(5-p-chlorophenyl)-1,3-thiazol-2-yl]-1, 2, 4-triazine derivatives containing a thiazole ring were synthesised as potential antitumor agents. Methods: Cytotoxicity of compounds (3) and (4) were evaluated in human hepatocellular carcinoma (HCC) cell lines (HepG2); compound (3) showed more cytotoxicity (IC50=9.0μg/ml) than compound (4) (IC50=18.40μg/ml) using doxorubicin as standard. The degree of toxicity of compound (3) was assessed by the LD50 with its anticancer performance by suppressing tumor angiogenesis against diethyl nitrosamine (DENA) induced hepatocellular carcinoma (HCC) in male rat model. Results : Carcinogenic rats showed a significant increase in markers of angiogenesis, tumour growth, and liver function tests and malondialdehyde level coupled by reduced hepatic glutathione level and caspase-3 activity. The distribution of compound (3) to animals after the development of HCC improved biochemical alterations from a DENA chemical carcinogen that is confirmed by hepatic histopathology. Conclusion: Compound 3 perhaps utilized as a strong applicant for newly therapeutic protocols against hepatocarcinogenesis by controlling tumor angiogenesis and renovating the activity of hepatic marker enzymes in addition reversing the oxidant-antioxidant imbalance in corporation with amelioration of histopathology. While the trial supports the use of compound 3 for improved HCC outcome and the toxicity and side effect should be considered.

Star-shaped Triazine-derivatives: would they crossbind SARS-CoV-2 spike helices?

This work describes synthesizable water-soluble Triazine-derivatives computationally crossbinding the S spike helices of Severe Acute Respiratory Syndrome coronavirus (SARS)-CoV-2. The "spring-loaded switch-folding” (S-SLSF) α-helices included in the S homotrimer top-to-bottom cavity and implicated in viral-host membrane fusion were targeted by star-shaped Trihydroxyl-Triphenyl-Triazines (TTT) leads at subnanomolar binding-scores. Exploration of in silico leads among millions of molecular candidates, included several similar searches, core-replacement, fragment extensions, or convolutional neural network deep-screening combined with hundreds of water-soluble lead-derivatives identified by manual iterations and commercially available building-blocks for chemical synthesis. The lead-derivatives are briefly discussed for in vitro validation and possibilities of fusion inhibition substituting mutations.