# Carbazole Derivatives as STAT Inhibitors: An Overview  
[PERSON]  
1 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria,  
87036 Arcavacata di Rende, Italy; [EMAIL_ADDRESS]
2 Department of Pharmacy-Pharmaceutical Sciences, University of Bari [PERSON], 70126 Bari, Italy; [EMAIL_ADDRESS] (A.B.); [EMAIL_ADDRESS] (A.C.)
3 Department of Science, University of Basilickata, 85100 Potenza, Italy; [EMAIL_ADDRESS] (G.S.); [EMAIL_ADDRESS] (G.  
psychotropic, anti-inflammatory, antihistaminic, antibiotic, and antioxidant activities [15]. However, carbazole application is not limited to the biological and pharmaceutical field. In fact, due to their properties, they are also employed in the materials science field, as optoelectronic materials, conducting polymers, and synthetic dyes [16; 17]. For instance, polyvinylcarbazoles (PVK) [18] have been thoroughly investigated for their employments in photorefractive materials and xerography. In fact, some poly (2,7-carbazole) derivatives (Figure 2) have been used in polymer solar cells [19]. The broad spectrum of their usage includes organic light-emitting diodes as green, red, and white emitters and some substituents at C-2, -3, -6, -7, and -9 positions can be responsible for these molecular and optical properties [20].  
Many natural carbazoles and their synthetic derivatives contain different substituents on the carbazole ring such as carbazomycin B (**4**) and carbazomadurin A (**5**), while others present a quadricyclic or pentacyclic structure, such as ellipticine (**6**) and staurosporine (**7**) respectively, or can appear as dimers, for example clausenamine A (**8**) (Figure 3) [21].  
Due to the growing interest in carbazole bioactivities, different synthetic strategies have been set up and reported in the literature [14; 22; 23]. [PERSON] et al. [14] thoroughly reviewed the preparation methods of these carbazole alkaloids. Usually, the synthetic  
Figure 1: Structure of carbazole (**1**) and murrayanine (**2**).  
Figure 3: Structures of: carbazomycin B (**4**), carbazomadurin A (**5**), ellipticine (**6**), staurosporine (**7**), clausenamine A (**8**).  
Figure 2: Poly (2,7-carbazole).  
routes to carbazoles include nitrene insertion, Fischer indolization, Pummerer cyclization, Diels-Alder reaction, dehydrogenase cyclization of diarylamines, etc. However, more recently, researchers explored the possibility of using transition metal-mediated C-C and C-N bond formation, cyclotrimeration, benzannulation, Suzuki-Miyaura coupling, and ring-closing metathesis [24; 25; 26].  
Several studies aimed to compare the structural characteristics of natural carbazole alkaloids. They underlined that 3-methylcarbazole (**9**, Figure 4) could be the essential intermediate in their biosynthesis in higher plants. By contrast, 2-methylcarbazole (Figure 4) could be the communal biogenetic precursor to the tricyclic carbazoles isolated from lower plants. Nevertheless, the natural precursor of the carbazole nucleus has not yet been identified.  
Concerning their biological activity, many research groups assessed the antiproliferative-active action of carbazoles against different types of tumor cells such as breast, cervical, ovarian, hepatic, oral cavity, and small-cell lung cancer [27; 28; 29; 30]. One of the principal mechanisms possibly involved in this effect is the ability of carbazoles to target the signal transducers and activators of transcription (STATs) family of signaling pathways (especially STAT3). Indeed, this class of proteins is fundamental for the growth and survival of different human tumor cells [31; 32]. In this context, the review aims to examine the studies carried out over the years to develop carbazolic compounds able to act on this target.