Synthesis and biological evaluation of novel imidazole nucleosides as potential anti-dengue virus agents

Targeting viral genome synthesis as broad-spectrum approach against RNA virus infections

“…68 In contrast to RBV and reminiscent of 6-chloropurine ribonucleotide, 69 EICAR ir reversibly inhibits IMPDH by covalently alkylating an active-site cysteine residue in a Michael-type addition. 70 And with RBV’s clinical impact as anti-HCV treatment, more analogues based on this molecular scaffold continue to emerge, such as ETAR or IM-18, 71,72 aiming for the development of pan-flavivirus inhibitors with enhanced potency or reduced cytotoxicity. 73…”

“…68 In contrast to RBV and reminiscent of 6-chloropurine ribonucleotide, 69 EICAR irreversibly inhibits IMPDH by covalently alkylating an active-site cysteine residue in a Michael-type addition. 70 And with RBV's clinical impact as anti-HCV treatment, more analogues based on this molecular scaffold continue to emerge, such as ETAR or IM-18, 71,72 aiming for the development of pan-flavivirus inhibitors with enhanced potency or reduced cytotoxicity. 73 In RBV and some of its close analogues, the carboxamide-moiety in the nucleobase-part ( Figure 3) with its rotational flexibility enables the analogues to mimic not only inosine and guanosine but also adenosine nucleotides; hence, these compounds are recognized by different enzymes of host purine metabolism (in Figures 2 and 3, note that adenosine kinase catalyzes RBV's monophosphorylation while RBV-MP inhibits IMPDH as IMP analogue; this feature also results in what was termed 'ambiguous base pairing' which will be discussed in the following section).…”

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

“…Nearly two-thirds of the main small molecule drugs have a minimum one aza heterocyclic fragment in their design structures [117]. Whereas nitrogen-based synthetic heterocyclic compounds provide broad therapeutic applications in several medical categories, such as VEGFr-2 inhibitors (91) [118], anti-cancer [119], anti-tubulin (92) [120], anti-inflammatory [121], antiaging [122], anti-tumor (93) [123], anti-influenza [124], anti-tubercular [125], anti-bacterial [126], anti-diabetic [127], anti-dengue virus [128], anti-convulsant and antidepressant [129], promising antioxidant, antifungal and anti-acetylcholinesterase agents (94) [130]. Moreover, they have been widely found as a key structural material and dominate the field of dyestuff synthesis [131], agro-based chemicals [132] and supramolecular chemistry [133].…”

“…Further, it is used as a solvent for resins and terpenes which are used in paint manufacturing as well as for metallic corrosion inhibition, due to its combination of high electron density [174]. There are a number of natural products (126)(127)(128)(129) with quinoline skeleton isolated from different plant species which are used as a medicine or employed as a lead molecule for the development of newer and potent molecules [175]. Furthermore, several quinoline derivatives have been found to be used as agrochemicals as well as in the processing of dyes, food colorants and pH indicators as well as in the synthesis of other organic substances [176].…”

Mechanisms of Csp3‐H or Nsp2‐H functionalization of 2,3‐diaminoindoles with triplet O2: A density functional theory investigation

“…[ 1 ] Among them, imidazolo‐indole framework has received growing attentions in recent years because of its fused heterocyclic skeleton involved in a large number of natural products and as drug candidate. [ 2 ] Several of their synthetic analogues have many biological properties, that is, antiinflamatory, [ 3 ] antimicrobial, [ 4 ] anticancer, [ 5 ] antitubercular, [ 6 ] antidengue, [ 7 ] anti‐analgesic, [ 8 ] anthelmintic, [ 9 ] antimycotic, [ 10 ] antitumor, [ 11 ] and antibacterial activities. [ 12 ] Also, the imidazole nucleus has displayed an important role in some advanced technology fields such as biological imaging, [ 13 ] glucagon receptors, [ 14 ] fluorescence labeling agents, [ 15 ] modulators of P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR), [ 16 ] and chromophores for nonlinear optic systems (NLOS).…”