Design, Synthesis, and Antifungal Evaluation of Cryptolepine Derivatives against Phytopathogenic Fungi

Abstract

Inspired by the widely antiphytopathogenic application of diversified derivatives from natural sources, cryptolepine and its derivatives were subsequently designed, synthesized, and evaluated for their antifungal activities against four agriculturally important fungi Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, and Sclerotinia sclerotiorum. The results obtained from in vitro assay indicated that compounds a1–a24 showed great fungicidal property against B. cinerea (EC50 < 4 μg/mL); especially, a3 presented significantly prominent inhibitory activity with an EC50 of 0.027 μg/mL. In the pursuit of further expanding the antifungal spectrum of cryptolepine, ring-opened compound f1 produced better activity with an EC50 of 3.632 μg/mL against R. solani and an EC50 of 5.599 μg/mL against F. graminearum. Furthermore, a3 was selected to be a candidate to investigate its preliminary antifungal mechanism to B. cinerea, revealing that not only spore germination was effectively inhibited and the normal physiological structure of mycelium was severely undermined but also detrimental reactive oxygen was obviously accumulated and the normal function of the nucleus was fairly disordered. Besides, in vivo curative experiment against B. cinerea found that the therapeutic action of a3 was comparable to that of the positive control azoxystrobin. These results suggested that compound a3 could be regarded as a novel and promising agent against B. cinerea for its valuable potency.

Semi-Synthetic Analogues of Cryptolepine as a Potential Source of Sustainable Drugs for the Treatment of Malaria, Human African Trypanosomiasis, and Cancer

“…The reaction of 1 with NBS or NIS provides a more convenient route to 7- or 7, 9-brominated or iodinated semi-synthetic derivatives compared with total synthesis, although it is recognized that, as recently shown by Chen et al (2021) , greater compound diversity may be more easily achieved using total synthesis.…”

Enhanced Bioactivity of Pomegranate Peel Extract following Controlled Release from CaCO3 Nanocrystals

“…There is a growing interest in finding natural antimicrobial compounds as a valid and safe alternative to conventional chemical treatments for managing plants infections and postharvest fruit diseases [ 3 ]. More than 19000 different types of fungi could affect crops causing serious economic losses in hundreds of countries around the world, such as Phytophthora [ 16 ], Fusarium oxysporum for potatoes and tomatoes [ 17 ], Magnaporthe oryzae for rice [ 18 ], and Botrytis cinerea for different fruits [ 19 ]. Furthermore, postharvest phase is very crucial for fresh fruits and vegetables, resulting in substantial economic losses up to 25%, due to various pathogens.…”

“…Since penicillin discovery, utilization of natural compounds to control pathogens has become crucial not only in medicine but also as ecofriendly strategy for crops protection. There are included plant-incorporated protectants, botanical and microbial-derived chemicals, and also synthetic analogues [ 18 , 21 , 22 ]. Recent research has been focused on essential oils or complex mixtures plants extracts, composed of several secondary metabolites which act in an interesting synergistic way preventing resistance phenomena [ 23 ].…”

Groebke–Blackburn–Bienaymé multicomponent reaction coupled with unconventional Pictet–Spengler cyclization for the synthesis of imidazo[4,5‐b]pyridine fused polycyclic heterocycles

“…For example, an isoquinoline‐based alkaloid Columbamine 1 shows promising antiplasmodial and IDO1 inhibitory activity (Figure 1) [6–8]. Cryptolepine 2 and Quindoline 3 are the fused polycyclic indole alkaloids having antiplasmodial, antifungal, and anticancer properties [9–11]. (−)‐Fascaplycin 4 , a pentacyclic fused β‐carboline is known to inhibit the proliferation of small cell lung cancer cell lines at very low concentration [12].…”