The molecule CD200, described many years ago as a naturally occurring immunomodulatory agent, capable of regulating inflammation and transplant rejection, has attracted additional interest over the past years with the realization that it may also serve as an important marker for progressive malignancy. A large body of evidence also supports the hypothesis that this molecule can contribute to immunoregulation of, among other diseases, infection, autoimmune disease and allergy. New data have also come to light to characterize the receptors for CD200 (CD200R) and their potential mechanism(s) of action at the biochemical level, as well as the description of a novel natural antagonist of CD200, lacking the NH2-terminal region of the full-length molecule. Significant controversies exist concerning the relative importance of CD200 as a ligand for all reported CD200Rs. Nevertheless, some progress has been made in the identification of the structural constraints determining the interaction between CD200 and CD200R, and this information has in turn proved of use in developing novel small molecule agonists/antagonists of the interaction. The review below highlights many of these newer findings, and attempts to place them in the broad context of our understanding of the role of CD200-CD200R interactions in a variety of human diseases.

A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their tyrosinase and urease inhibitory activity. Evaluation of prepared derivatives demonstrated that compounds (8b) and (8j) are most potent mushroom tyrosinase inhibitors whereas all of the obtained compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (8a), (8f) and (8i) exhibited excellent enzyme inhibitory activity with IC50 0.037, 0.044 and 0.042 μM, respectively, while IC50 of thiourea is 20.9 μM.

This review focuses on the cytotoxic effect of new synthetic pyrazolo[4,3-e][1,2,4]triazine derivatives against different tumor cell lines. Some annulated pyrazolotriazines i.e., pyrazolo[4,3-e][1,2,4]triazolo[4,3-b][1,2,4]triazines and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine demonstrated significant broad cytotoxic activity in micromolar range concentration, which could have excellent potential to be new candidate therapeutic agents in cancer chemotherapy.

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

The over expression of melanogenic enzymes like tyrosinase caused many hyperpigmentaion disorders. The present work describes the synthesis of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives 3a-e and 5a-e as antimelanogenic agents. The tyrosinase inhibitory activity of synthesized derivatives 3a-e and 5a-e was determined and it was found that derivative 5c possesses excellent activity with IC 50 ¼ 0.0089 mM compared to standard kojic acid (IC 50 ¼ 16.69 mM). The presence of hydroxyl groups at the ortho and the para position of cinnamic acid phenyl ring in compound 5c plays a vital role in tyrosinase inhibitory activity. The compound 5d also exhibited good activity (IC 50 ¼ 8.26 mM) compared to standard kojic acid. The enzyme inhibitory kinetics results showed that compound 5c is a competitive inhibitor while 5d is a mixed-type inhibitor. The mode of binding for compounds 5c and 5d with tyrosinase enzyme was also assessed and it was found that both derivatives irreversibly bind with target enzyme. The molecular docking and molecular dynamic simulation studies were also performed to find the position of attachment of synthesized compounds at tyrosinase enzyme (PDB ID 2Y9X). The results showed that all of the synthesized compounds bind well with the active binding sites and most potent derivative 5c formed stable complex with target protein. The cytotoxicity results showed that compound 5c is safe at a dose of 12 mg/mL against murine melanoma (B16F10) cells. The same dose of 5c was selected to determine antimelanogenic activity; the results showed that it produced antimelenogenic effects in murine melanoma (B16F10) cells. Based on our investigations, it was proposed that compound 5c may serve as a lead structure to design more potent antimelanogenic agents.