Synthesis of Fused Indolo‐Pyrazoles and Their Antimicrobial and Insecticidal Activities against Anopheles arabiensis Mosquito

• Published in: ChemistrySelect (Weinheim) 2020-03, Vol.5 (9), p.2756-2762
• Main Authors: Makhanya, Talent R., Gengan, Robert M., Kasumbwe, Kabange
• Format: Article
• Language: English
• Subjects: [3+2] annulation reaction; anti-mosquito activity; antimicrobial activity; indolo-pyrazole
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201904620

A new approach was used for the synthesis of novel fused indolo‐pyrazoles (FIPs). Indole, arylhydrazine and benzaldehyde derivatives were used for the [3+2] annulation reaction in one‐pot system. The compounds were characterised by 1H NMR, 13C NMR, 2D NMR, MS and elemental analysis. The in vitro antifungal activity of the FIPs were evaluated against Candida albicans, Candida utilis, Saccharomyces cerevisiae, Aspergillus flavus and Aspergillus niger. Two FIPs, viz. N‐methyl‐3‐phenyl‐2, 3‐dihydropyrazolo [3, 4‐b] indole‐1(4H)‐carbothioamide (8 r) and 3‐(4‐methoxyphenyl)‐N‐methyl‐2,3‐dihydropyrazolo[3,4‐b]indole‐1(4H)‐carbothioamide (8 x) displayed good antifungal activity against Saccharomyces cerevisiae with a zone of inhibition diameter of 23 and 20 mm, respectively. They also displayed substantial potency against Saccharomyces cerevisiae with the MIC of 0.18 μM. All FIPs were screened for larvicidal and insecticidal properties against Anopheles arabiensis of which 12 FIPs produced more than 80 % larvae mortality at a 4 μg/mL dose in 24 hours whilst 8 FIPs showed a knock‐down of mosquitoes within the first 60 minutes of exposure, which was comparable to the positive control Temephos. Novel fused indolo‐pyrazoles (FIPs) were synthesized through [3+2] annulation reaction using one pot system. The reaction conditions were optimized and the best yield was obtained using acetonitrile with indium chloride as a catalyst. All synthesized compounds were characterised using spectroscopic techniques. FIPs displayed good antifungal activity against Saccharomyces cerevisiae and also produced more than 80 % larvae mortality at a 4 μg/mL dose in 24 hours whilst 8 FIPs showed a knock‐down of mosquitoes within the first 60 minutes of exposure against Anopheles arabiensis.