Starting from pinane-, apopinane- and carane-based 1,3-amino alcohols obtained from monoterpene-based β-amino acids, a library of monoterpene-fused 2-imino-1,3-thiazines as main products and 2-thioxo-1,3-oxazines as side-products were prepared via two- or three-step syntheses. When thiourea adducts prepared from 1,3-amino alcohols and aryl isothiocyanates were reacted with CDI under mild conditions, O-imidazolylcarbonyl intermediates were isolated which could be transformed to the desired 1,3-thiazines under microwave conditions. 1,3-Thiazines and 2-thioxo-1,3-oxazine side-products could also be prepared in one-step reactions through the application of CDI and microwave irradiation. The ring-closure process was extended to cycloalkane-based γ-hydroxythioureas. The carane- and apopinane-based derivatives exhibited marked antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, A2780, MCF7 and A431).

A modular and functional group-tolerant protocol for the transition metal-free coupling of novel N,O- and N,S-heterocyclic vinyl chlorides with terminal acetylenes and styrenes has been developed, leading to the epimerization-free synthesis of fully carbofunctionalized dihydro-1,4-oxazines/thiazines. Bicyclic morpholines have also been prepared through the interrogation of newly synthesized cross-conjugated dienes in Diels-Alder reactions. The use of environmentally benign reaction media endows the current strategy with a practical advantage.

A series of novel heterocyclic structures, namely 1,3-oxazines, 1,3-thiazines and 2,4-diaminopyrimidines, were designed and synthesised. The bioassay tests demonstrated that, among these analogues, 2,4-diaminopyridine derivatives showed significant antiproliferative activity against different human cancer cell lines (A2780, SiHa, HeLa, MCF-7 and MDA-MB-231). Pyrimidines substituted with N2 -(p-trifluoromethyl)aniline, in particular, displayed a potent inhibitory effect on the growth of cancer cells. Structure-activity relationships were also studied from the aspects of stereochemistry on the aminodiol moiety as well as exploring the effects of substituents on the pyrimidine scaffold.

In this article, we showed the synthesis of new polycyclic aromatic compounds, such as thienotriazolopyrimidinones, N-(thienotriazolopyrimidine) acetamide, 2-mercapto-thienotriazolo-pyrimidinones, 2-(((thieno-triazolopyrimidine) methyl) thio) thieno-triazolopyrimidines, thieno-pyrimidotriazolo-thiazines, pyrrolo-triazolo-thienopyrimidines, thienopyrimido-triazolopyrrolo-quinoxalines, thienopyrimido-triazolo-pyrrolo-oxathiino-quinoxalinones, 1,4-oxathiino-pyrrolo- triazolothienopyrimidinones, imidazopyrrolotriazolothienopyrimidines and 1,2,4-triazoloimidazo- pyrrolotriazolothienopyrimidindiones, based on the starting material 2,3-diamino-6-benzoyl-5- methylthieno[2,3-d]pyrimidin-4(3H)-one (3). The chemical structures were confirmed using many spectroscopic ways (IR, 1H, 13C, -NMR and MS) and elemental analyses. A series of thiazine, imidazole, pyrrole, thienotriazolopyrimidine derivatives were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines, i.e., CNE2 (nasopharyngeal), KB (oral), MCF-7 (breast) and MGC-803 (gastric) carcinoma cells. The compounds 20, 19, 17, 16 and 11 showed significant cytotoxicity against types of human cancer cell lines.

Over the past decade, thiazines, thiadiazoles, and thiohydrazides have attracted increasing attention due to their sedative, antimicrobial, antiviral, antifungal, and antitumor activities. The clinical efficacy of such drugs, as well as the possibility of developing resistance to antimicrobials, will depend on addressing a number of fundamental problems, including the role of membrane lipids during their interaction with plasma membranes. The effects of the eight 1,3- thiazine-, 1,2,3,4- dithiadiazole-, and thiohydrazide-related compounds on the physical properties of model lipid membranes and the effects on reconstituted ion channels induced by the polyene macrolide antimycotic nystatin and antifungal cyclic lipopeptides syringomycin E and fengycin were observed. We found that among the tested agents, the fluorine-containing compound N'-(3,5-difluorophenyl)-benzenecarbothiohydrazide (C6) was the most effective at increasing the electric barrier for anion permeation into the hydrophobic region of the membrane and reducing the conductance of anion-permeable syringomycin pores. A decrease in the membrane boundary potential with C6 adsorption also facilitated the immersion of positively charged syringomycin molecules into the lipid bilayer and increases the pore-forming ability of the lipopeptide. Using differential scanning microcalorimetry, we showed that C6 led to disordering of membrane lipids, possibly by potentiating positive curvature stress. Therefore, we used C6 as an agonist of antifungals forming the pores that are sensitive to membrane curvature stress and lipid packing, i.e., nystatin and fengycin. The dramatic increase in transmembrane current induced by syringomycin E, nystatin, and fengycin upon C6 treatment suggests its potential in combination therapy for treating invasive fungal infections.