A rapid and scalable microwave-assisted strategy for the synthesis of neocryptolepine and its analogues: Comprehensive bioactivity profiling.

A rapid synthesis of neocryptolepine and its analogues have been developed using 2-Bromo-1H-indole-3-carbaldehydes and N-methylanilines as starting materials under microwave irradiation. A total of 14 different 5-methyl-5H-indolo[2,3-b]quinoline derivatives containing 7 novel analogues of neocryptolepine have been synthesized. The method has also been used for gram-scale (1.03 g) synthesis of neocryptolepine starting from 1.02 g of Bromoindolecarbaldehyde. The synthesized compounds were evaluated in vitro for their antidiabetic, anti-inflammatory, antioxidant, and antibacterial activities. The obtained results suggest that the compound 1ad exhibits comparable antidiabetic activity, inhibiting α-amylase and α-glycosidase. The natural product neocryptolepine revealed the best anti-inflammatory and antioxidant activity, compared to the standards diclofenac and ascorbic acid, respectively. Among all the derivatives evaluated for antibacterial activity in vitro against Gram-positive bacteria (S. aureus and S. pyogenes) and Gram-negative bacteria (S. typhi and P. aeruginosa), neocryptolepine exhibits the maximum antibacterial potency, with MIC values ranging from 0.25 to 0.5 μg/mL against all four strains. These MIC values were slightly lower than those observed for streptomycin (0.5-2 μg/mL), and comparable to Ciprofloxacin (0.125-2 μg/mL), with slightly enhanced antibacterial efficacy for gram-positive bacteria compared to gram-negative bacteria.