Mechanosynthesis of Triazolyl‐bis(indolyl)methane Pharmacophores via Gold Catalysis: A Prelude to Their Molecular Electronic Properties and Biological Potency

Abstract

Dedicated to Prof. Carsten Bolm for his significant contributions in the area of mechanochemical organic synthesis.Chemical structures possessing both 1,2,3-triazole and bis(indolyl)methane fragments gained considerable interest in drug synthesis owing to their established biological efficacies. However, 1,2,3-triazoles linked at the bridging position of bis(indolyl)methane is a logical and unexplored design approach. In this regard, nine new triazolyl-bis(indolyl)methane conjugates under AuCl catalyzed ball-milling conditions were accomplished. Comparative evaluation on absorptive and emissive properties of the synthesized dyads were also analyzed. To unravel the influence of different peripheral substituents on the electronic structure and π-orbital properties, theoretical investigations were performed. Screening of molecules for free radical scavenging, anti-inflammatory and antidiabetic showed comparable potency against reference drugs. In particular, compounds 7 h, 7 d and 7 a displayed good efficiency of α-amylase inhibition. The DNA gyrase inhibitory potential of all compounds were assessed in silico which revealed high binding affinity (ΔG = À 8.99 Kcal/mol) for 7 i followed by 7 h (ΔG = À 7.80 Kcal/mol) with the targeted protein.

Synthesis and Experimental Structure of a Multifunctional Catechol‐Azomethinebenzoic Acid, DFT/DMol3 Calculations, and Molecular Docking with Hsp90

“…The so‐called chemical reactivity descriptors, which we have detailed in previous publications, [50,51] have been widely used to understand and predict the chemical behavior of compounds [52–55] . They are essentially calculated from the energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) using the Equations (1)–8 [50–55] …”

“…energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) using the Equations ( 1)-( 8). [50][51][52][53][54][55] Energy gap ðEgÞ,…”

Synthesis and Optoelectronic Features of Rhodamine‐Triazole Dyads as Metallochromic Probes for Copper‐Selective Chemosensing

“…As shown in Scheme 1, we commenced the synthesis of rhodamine hydrazide (1) by the Et 3 N promoted spirocyclization of rhodamine 6G (Rh-6G) followed by condensation with hydrazine. [44] As part of our continuing endeavor on triazole chemistry, [45][46][47][48][49] we intended to prepare the requisite triazole precursors by taking advantage of our recently developed mechanochemical click chemistry. [45] Therefore, three triazole aldehydes (4 a-c) were synthesized by CTAB catalyzed annulation between (E)-cinnamaldehyde (2) and benzylic azides (3 a-c) under ball-milling conditions.…”

Homogeneous Gold Catalysis for Regioselective Carbocyclization of Alkynyl Precursors

“…Accordingly, it leaves a space for another review focusing exclusively on gold catalyzed regioselective cyclization between alkynes and a tethered nucleophilic carbon. As part of our continuing journey in gold catalyzed approaches [70–88] along with highlighting their regiochemical outcomes, [32–36] we herein disclose the regioselective carbocyclization of alkynyl precursors enabled by catalytic gold chemistry.…”