Analysis on the traditional Chinese medicine syndromes and Six-Meridian Pattern Identification of coronavirus disease 2019

Zhongjing Zhang’s Shang Han Lun(Treatise on Cold-induced Diseases,an ancient Chinese medical book written by Zhongjing Zhang in the Eastern Han Dynasty)was pioneering to conduct the Six-Meridian Pattern Identification,which provided later generations with a theoretical basis for the treatment of Exogenous Febrile Diseases.The coronavirus disease 2019 belongs to the category of“Pestilence”(the general term for virulent infectious epidemic diseases)in“Febrile Diseases”(the general term for acute externally contracted diseases caused by Warm Pathogens,with fever as the chief manifestation,also known as Warm Diseases)and the treatment of coronavirus disease 2019 is mostly based on the Triple Energizer Pattern Identification(the a categorization of Pattern Identification according to the theory of the Triple Energizer)or Defense,Qi,Nutrient and Blood Pattern Identification(the categorization of Febrile Diseases Pattern Identification according to the theory of Defense,Qi,Nutrient and Blood which indicates the stages of the clinical course with corresponding pathological changes).Although the theory of Cold-induced Diseases(the condition caused by Cold,manifested as chills and fever,absence of sweating,headache and floating-tense pulse)and the theory of Febrile Disease seem to be entirely distinct with each other,Zhongjing Zhang’s theory contained Triple Energizer Pattern Identification or Defense,Qi,Nutrient and Blood Pattern Identification,and Triple Energizer Pattern Identification or Defense Qi,Nutrient and Blood Pattern Identification also contained Zhongjing Zhang’s Six-Meridian Pattern Identification(the categorization of Pattern Identification according to the theory of the Six Meridians,applied to the diagnosis of acute Febrile Diseases at different stages,and also useful for the Pattern Identification of other diseases).The basic principles and therapeutic methods of Cold-induced Diseases and Febrile Diseases are intertwined.Therefore,this paper will combine the two theories to analyze the traditional Chinese medicine syndromes of coronavirus disease 2019,and try to use Six-Meridian Pattern Identification to guide the treatment of this disease.

Design, synthesis and insecticidal activities of novel 1-substituted-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives

A series of novel 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives（6a–6n, 7a, 7b, and 8a-8f）were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.

Synthesis and bioactivities of novel 2-(thioether/sulfone)-5-pyrazolyl-1,3,4-oxadiazole derivatives

By introducing the pyrazole moiety into the 5-position of 1,3,4-oxadiazole,a series of novel 2-（thioether/sulfone）-5-pyrazolyl-l,3,4-oxadiazole derivatives were synthesized.Preliminary bioassays suggested that target compounds exhibited appreciable activity against pathogenic bacteria Xanthomonas oryzae pv.oryzae（Xoo） and five phytopathogenic fungi in vitro.Among them,the half-maximal effective concentration（EC_（50）） values of 6c,7a,7b and 7c against Xoo were within 16.6 μg/mL and 65.7 μg/mL,which were better than those of commercial agricultural antibacterial bismerthiazol（92.6 μg/mL） and thiodiazole copper（121.8 μg/mL）.While compounds 7a,7b,and 7c exerted comprehensive antifungal activity toward five plant fungi,which were comparable with that of hymexazol.The results demonstrated that this kind of compounds can be further studied and developed as promising antifungal and antibacterial agents.

Synthesis, Antimicrobial Activity, and Molecular Docking of Benzoic Hydrazide or Amide Derivatives Containing a 1,2,3-Triazole Group as Potential SDH Inhibitors

The present study was carried out in an attempt to synthesize a new class of antimicrobial agents containing a 1,2,3-triazole motif formed by classical copper catalyzed click chemistry.Antifungal bioassay results showed that five compounds 5a;5e,5h,5j,and 5k possessed a remarkable growth inhibitory activity against Botryosphaeria dothidea,Rhizoctonia solani and Gibberella zeae with EC_(50) values within 10.0-0.306μg/mL.The in vitro efficacy was better than those of the commercial agrochemicals Azoxystrobin,Boscalid,and Fluxapyroxad.In vivo trials showed that compound 51 was effective for the control of rice sheath blight and wheat scab with the effects of 75% and 95%,respectively.Antifungal mechanism studies suggested that target compounds were potential succinate dehydrogenase inhibitors(SDHIs),which were proposed by the agreeable molecular docking study and restrained SDH activity(IC_(50)=3.95 μg/mL,51).Interestingly,compounds 5r and 5s displayed good antibacterial activity against phytopathogens.In vivo screening of 5r and 5s against rice bacterial blight afforded a superior control effect(up to 51%)than those of commercial agents Bismerthiazol and Thiodiazole copper.The current studies could support some title compounds to be the lead compounds for exploring highly bioactive antimicrobial substrates,particularly the potential SDHIs.