Synthesis and comparison of substituted 1,2,3-dithiazole and 1,2,3-thiaselenazole as inhibitors of the feline immunodeficiency virus (FIV) nucleocapsid protein as a model for HIV infection

Abstract

We report the first biological evaluation the 1,2,3-thiaselenazole class of compound and utilising a concise synthetic approach of sulfur extrusion, selenium insertion of the 1,2,3-dithiazoles. We created a small diverse library of compounds to contrast the two ring systems. This approach has highlighted new structure activity relationship insights and lead to the development of sub-micro molar anti-viral compounds with reduced toxicity. The 1,2,3-thiaselenazole represents a new class of potential compounds for the treatment of FIV and HIV.

Antimicrobial and Antifungal Activity of Rare Substituted 1,2,3-Thiaselenazoles and Corresponding Matched Pair 1,2,3-Dithiazoles

“…The 1,2,3-dithiazole core has provided a number of interesting medicinal chemistry applications (Figure 1). In fact, 1,2,3-dithiazole scaffold has a broad biological activity profile which includes inhibition of cancer (1−3), [13][14][15] bacteria (4,5), [13,[16][17][18][19] fungus (6,7) [19][20][21][22][23][24], virus [25,26] and melanin [27]. Although not definitively proven in most cases it is thought that most of these activities have centered around a cysteine-activated nucleophilic attack.…”

“…Although not definitively proven in most cases it is thought that most of these activities have centered around a cysteine-activated nucleophilic attack. With this mechanism in mind and previous success modulating that activity of 1,2,3-dithiazole, we also screened the corresponding 1,2,3-thiaselenazole analogs [13,25,26]. This was done to improve potency by weakening the S-S bond by elongation to more diffuse S-Se bond, while being careful to not compromise the toxicity profile of the compounds [26].…”

Synthesis of Various Derivatives of [1,3]Selenazolo[4,5‐d]pyrimidine and Exploitation of These Heterocyclic Systems as Antibacterial, Antifungal, and Anticancer Agents

“…[2] In addition, it plays a pivotal role in the activity of various enzymes such as thioredoxin reductase, iodothyronine deiodinase, selenophosphate synthetase, and selenoprotein P. [3][4][5][6][7] Based on a large variety of chemical, physical, and biological properties associated with the presence of selenium, the synthesis of many Se-containing heterocycles has been developed as a very active research area. [8,9,18,[10][11][12][13][14][15][16][17] A diversity of organic selenium derivatives has earned well-deserved reputation for effective biocidal, [19,20] antifungal, [21][22][23][24] antiinflammatory, [25] anti-HIV, [26][27][28] antioxidant, [23,[29][30][31][32][33][34] free radical scavenging, [29,31,33,[35][36][37][38] antimicrobial, [22,24,39] anticonvulsant, [39] histone deacetylase …”

Synthesis of 2-((2-(Benzo[d]oxazol-2-yl)-2H-imidazol-4-yl)amino)-phenols from 2-((5H-1,2,3-Dithiazol-5-ylidene)amino)phenols through Unprecedented Formation of Imidazole Ring from Two Methanimino Groups

“…1,2,3-Dithiazoles are one of the most investigated groups of five membered sulfur–nitrogen heterocycles [ 1 , 2 , 3 ]. In addition to the utility of these heterocyclic compounds as potent biologically active compounds [ 4 , 5 , 6 , 7 , 8 ], they are efficient precursors for functional materials applied in electronics and spintronics [ 9 , 10 , 11 , 12 , 13 , 14 ]. The chemistry of monocyclic 1,2,3-dithiazoles has attracted considerable attention through recent decades [ 1 , 2 , 3 ] due to the easy availability of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel’s salt, 1 ) [ 15 , 16 ].…”