Design, Synthesis, and Antiviral, Fungicidal, and Insecticidal Activities of Tetrahydro-β-carboline-3-carbohydrazide Derivatives

Abstract

According to our previous research on the antiviral activity of β-carboline and tetrahydro-β-carboline derivatives, using (1S,3S)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carbohydrazide (1) as a lead compound, series of novel tetrahydro-β-carboline derivatives containing acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. Most of these compounds exhibited excellent antiviral activity both in vitro and in vivo. The in vivo inactivation, curative, and protection activities of compounds 8, 9, 12, 16, 28, 29, and 30 were much higher than that of ribavirin (37.6%, 39.4%, and 37.9% at 500 μg/mL) and the lead compound (40.0%, 42.3%, and 39.6% at 500 μg/mL). Especially, the in vitro and in vivo activities of compound 16 (36.9%, 33.6%, 30.2%, and 35.8%) at 100 μg/mL, which were very close to that of ribavirin (40.0% for in vitro activity) at 500 μg/mL. Compounds 9 and 29 were chosen for the field trials of antiviral efficacy against TMV (tobacco mosaic virus); the results exhibited that both compounds, especially compound 29, showed better activities than control plant virus inhibitors. At the same time, the fungicidal results showed that compounds 6, 9, and 11 exhibited good fungicidal activities against 14 kinds of phytopathogens. Additionally, compounds 3 and 23 exhibited moderate insecticidal activity against the four tested species of insects.

Leveraging botanical resources for crop protection: the isolation, bioactivity and structure–activity relationships of lycoris alkaloids

“…When caranine (6) was reacted with SOCl 2 , we expected the C-1 hydroxyl group to be replaced by chloride. However, the reaction gave anhydrocaranine (7) as an eliminated product. A similar phenomenon was also observed by Takeda 38 using POCl 3 as the halogenating agent.…”

“…Lycorine derivatives 3-17 were investigated for their anti-TMV activity. Table 1 shows that when the OH was converted to AcO (3, 4a, 4, 10, and 11a) or Cl (5a), carbonyl (9) or OCH 3 (10), or when the OH was removed (6,7,8,11), the anti-TMV activity of the lycorine derivatives was decreased. However, when the two OH groups were converted to epoxy (12) or eliminated to form the aromatization compound (13), the activities were almost unchanged.…”

“…However, aromatizing the D ring and opening the benzodioxole group may be favourable for the retention of activity. (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) were also investigated for their insecticidal activities against the diamondback moth (P. xylostella) and mosquito (C. pipiens pallens) was aromatized, the compounds showed excellent insecticidal activities against both P. xylostella and C. pipiens pallens. Tables 6 and 7, many lycorine analogues showed good inhibitory activities (inhibition rate > 80%) at a concentration of 50 mg L −1 .…”

“…However, the invalid assumption that ‘natural is safe – synthetic is hazardous’ is deeply ingrained in the public mindset due to the demonstrated negative environmental and health impacts of first‐generation synthetic pesticides (organochlorines, organophosphates, carbamates) . Because of the increasing pressure to provide safe food and the increasingly stringent regulatory requirements of food production, there is a critical need to discover and develop more environmentally benign and less hazardous pesticides; botanical pesticides have become the preferred green choice due to their perceived low risk to the environment and safety toward non‐target organisms …”

“…3,4 Because of the increasing pressure to provide safe food and the increasingly stringent regulatory requirements of food production, there is a critical need to discover and develop more environmentally benign and less hazardous pesticides; botanical pesticides have become the preferred green choice due to their perceived low risk to the environment and safety toward non-target organisms. [5][6][7] However, botanical pesticides are often used as crude plant extracts, which means that they comprise a mixture of several secondary metabolites. In many cases, the crude extracts have not been systematically tested for their agricultural activities; nor have the structures of their active compounds been clarified, which makes further development difficult due to lack of information.…”