Compounds Ia Research Articles

Synthesis and Tyrosinase Inhibitory Activity of Metronidazole Derivatives

A series of metronidazole esters have been synthesized starting from metronidazole and various aromatic and aliphatic carboxylic acids using coupling agents such as DCC/DMAP or DIPEA. The synthesized compounds were thoroughly characterized by various spectral data. The melanogenesis activity was determined in mushroom tyrosinase by the oxidation of 3,4-dihydroxyphenylalanine in the presence of the compounds at buffered pH = 6.5 with kojic acid as standard. Among the synthesized compounds, Ia, Ib, and Ih showed moderate activity when compared with the standard IC50 values 94.8, 118.8, and 139,8 ?M, respectively. Molecular docking studies performed with 2y9w protein exhibited a greater number of physical interactions for compounds Ia, Ib, and Ih confirming the mushroom tyrosinase activity.. KEYWORDS :Inhibitors, Melanogenesis, Metronidazole ester, oMlecular docking, Tyrosinase activity.

Construction of new oxime esters of cholesterol containing piperic acid-like fragments as insecticidal agents against Aphis citricola Van der Goot (Homoptera: Aphididae) and Plutella xylostella Linnaeus (Lepidoptera: Plutellidae)

In order to application of cholesterol as pesticidal agents, a series of oxime esters of cholesterol containing piperic acid-like fragments were semi-synthesized by modification of cholesterol at the C-3 and C-6 positions. Their structures were characterized by 1H NMR, HRMS and mp, and their purity was determined by HPLC. Against Aphis citricola Van der Goot, derivatives Ib (R = 4-FPh) and In (R = 3,4-ethylenedioxystyryl) exhibited 5.0 and 4.8 folds more pronounced aphicidal activity of their precursor cholesterol. Against Plutella xylostella Linnaeus, compounds Ia (R = Ph) and If (R = 3,4-methylenedioxyphenyl) showed 2.2 and 2.0 folds more potent insecticidal activity of cholesterol. Their SARs were also observed.

The influence of soil chemistry on branched tetraether lipids in mid- and high latitude soils: Implications for brGDGT- based paleothermometry

Branched glycerol dialkyl glycerol tetraethers (BrGDGTs) are a suite of orphan bacterial membrane lipids commonly used as paleo-environmental proxies for mean annual air temperature (MAT) and pH. Recent calibrations between the Methylation of Branched Tetraethers index (MBT′5ME) and MAT, based on modern surface soils (including peats), show a considerable amount of scatter, especially in mid- and high latitude soils, suggesting that brGDGT signals are influenced by additional environmental and/or biological controls at these sites. Here we test the impact of soil chemical gradients and bacterial community changes (16S rDNA sequence-based) on brGDGT distributions at two grasslands sites (Ossenkampen [NL], ForHot [IS]), and one agricultural site (Craibstone [UK]). In addition to the variation in soil chemistry, the ForHot site experiences belowground warming. Of the studied edaphic parameters, soil pH is the primary factor that explains simultaneous changes in both the bacterial community composition and the brGDGT distribution. Variations in the MBT′5ME at two sites without soil warming indeed correlate strongly to soil pH (r = 0.9–1.0, pH = 4.5–7.3), whereas pH explains part of the variation in the MBT′5ME at the site with soil warming (mean soil temperature ranging between 5 and 14 °C). At all sites, soil pH is positively related with the same brGDGTs (Ib, IIb, IIIb, IIIc, IIa′, IIb′, IIc′, IIIa′, IIb′, IIIc′) and influences the ratio between main brGDGT compounds Ia, IIa and IIIa, impacting the MBT′5ME values. This change in brGDGT distributions coincides with a change in the composition of the bacterial community at all sites. The bacterial clades that vary at the three experimental sites (specifically Acidobacteria subgroups 1, 2, 3, 6, 22) have previously been shown to also respond to soil pH on a global scale. As soil pH changes on geological timescales, the impact of changing pH on the MBT′5ME paleothermometer should be considered when performing paleoclimate studies.

Synthesis, extracorporeal nephrotoxicity, and 3D-QSAR of andrographolide derivatives.

Andrographolide is a traditional Chinese medicine monomer with many pharmacological activities, but has potential nephrotoxicity. Here, we aim to investigate the relationship between modification of andrographolide structure and its nephrotoxicity. Twenty-three andrographolide derivatives were synthesized, and their structures were confirmed by 1 H-NMR and HRMS. Nephrotoxicity of these compounds against human renal tubular epithelial (HK-2) cells was evaluated using the MTT assay. The results indicated that most of them had significantly reduced nephrotoxicity, especially compounds III, V, and IXc , with IC50 values of 1,985, 1,300, and 806.9μmol/L, respectively, which were obviously superior to andrographolide (IC50 30.60μmol/L). However, compounds Ia -If (IC50 values<30μmol/L), the 14-OH derivatives of andrographolide, showed higher nephrotoxicity than that of andrographolide. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models of COMFA and COMSIA were established (COMFA: q2 =0.639, r2 =0.951; COMSIA: q2 =0.569, r2 =0.857). This model allowed proposing five new compounds with lower theoretical nephrotoxicity, which would be worthwhile to synthesize and evaluate. We believe that predicted models will help us to understand the structural modification requirements of andrographolide to reduce the nephrotoxicity, and further investigations will be needed to determine the mechanism involved in the effect of less nephrotoxic compounds.

Design and Bioevaluation of Novel Hydrazide-Hydrazones Derived from 4-Acetyl-N-Substituted Benzenesulfonamide

In this research, a series of hydrazine-hydrazone derivatives (Ia–g), (IIa–h) were synthesized to discover new antioxidant and anticholinesterase agents. The structures of synthesized compounds were characterized by spectroscopic data using UV, IR, 1H, 13C NMR, mass spectroscopy, and elemental analysis. The bio-evaluation of the synthesized compounds (Ia–g), (IIa–h) were evaluated according to in vitro activity assays. The results of β-carotene/linoleic acid assay showed that among the synthesized compounds, the (Ib), (Ie), (IIb–IIe), and (IIh) compound exhibited higher activity for the lipid peroxidation inhibitory activity. In the DPPH free scavenging activity and the cation radical scavenging activity in ABTS•+ activity, compound (IIb) was found to be more active. In the CUPRAC reduced power assay, the A0.5 values of all synthesized compounds were better than α-TOC. In AChE assay, compound (IIb) exhibited the most activity with IC50 = 11.12 ± 0.74 µM, while the compounds (Ib–g) and (IIb–h), exhibited excellent activity than the positive standard galantamine (IC50 = 46.06 ± 0.10 μM) in the BChE assay.

Actoprotective activity research of 2-((5-(2-bromophenyl)-4-substituted-4H-1,2,4-triazole-3-yl)thio)acetates

Сильная усталость может возникнуть из-за переутомления, недостатка физических упражнений, депрессии, бессонницы и т. д. Следует понимать, что усталость, слабость (и эмоциональная, и физическая) не являются болезнью. Часто актопротекторные вещества используют для уменьшения усталости. Производные 1,2,4-триазола зарекомендовали себя для поиска новых веществ с широким спектром фармакологической активности. Цель работы – исследование актопротекторной активности среди ранее синтезированных 2-((5-(2-бромфенил)-4-замещенных-4 Н -1,2,4-триазол-3-ил)тио)ацетатов. Материалы и методы. Соединения, использованные для изучения фармакологической активности, синтезированы на кафедре естественных дисциплин для иностранных студентов и токсикологической химии Запорожского государственного медицинского университета. Для изучения актопротекторной активности 2-((5-(2-бромфенил)-4-замещенных-4 Н -1,2,4-триазол-3-ил)тио)ацетатов использовали белых нелинейных крыс весом 200–260 г, 7 животных на группу. Для исследования фармакологической активности использовали метод принудительного плавания с нагрузкой 10 % от веса крысы. Статистические результаты рассчитаны с использованием теста Колмогорова–Смирнова и теста Шапиро–Уилка. Результаты. Установлено, что соединения Ia, Ib, IIb, IIk, IIj имеют умеренный актопротекторный эффект, но ни одно соединение не превышает препарат сравнения. Сделано несколько выводов о зависимости «структура – актопротекторное действие»: самое активное соединение – 2-этаноламмоний 2-((5-(2-бромфенил)-4-этил-4 Н -1,2,4-триазол-3-ил)тио)ацетат (IIj); переход в 2-((5-(2-бромфенил)-4-замещенные-4 Н -1,2,4-триазол-3-ил)тио)ацетатные соли и выбор катиона (натрий, калий или 2-этаноламмоний) приводит к усилению актопротекторного эффекта. Выводы. В результате работы исследована актопротекторная активность 18 новых 2-((5-(2-бромофенил)-4-замещенных-4 Н -1,2,4-триазол-3-ил)тио)ацетатов. Сделаны выводы о зависимости «структура – актопротекторный эффект».

Cu(II), Ni(II), and Co(II) Complexes of Tetradentate Azomethine Ligands: Chemical and Electrochemical Syntheses, Crystal Structures, and Magnetic Properties

Complexes CuL1 ⋅ MeOH (Ia), NiL1 ⋅ MeOH (Ib), CоL1 ⋅ MeOH (Ic), CuL2 (IIa), NiL2 (IIb), and CоL2 (IIc) of the tetradentate azomethine compounds, namely, 4-methyl-N-[2-[(E)-2-[2-[2-[(E)-[2-(p-toluenesulfamino)phenyl]methyleneamino]ethoxy]ethyliminomethyl]phenyl]benzenesulfamide (H2L1) and 4-methyl-N-[2-[(E)-3-[4-[3-[(E)-[2-(p-toluenesulfamino)phenyl]methyleneamino]propoxy]butoxy]-propyliminomethyl]phenyl]benzenesulfamide (H2L2), which are the condensation products of 2-(N-tosylamino)benzaldehyde with 3,4-dioxa-1,8-octanediamine and 4,9-dioxa-1,12-dodecanediamine, are synthesized using the chemical and electrochemical methods. The structures, compositions, and properties of the synthesized metal complexes are studied by the methods of elemental analysis, IR spectroscopy, X-ray absorption spectroscopy, magnetochemistry, and X-ray diffraction analysis (СIF files CCDC nos. 1910746 (Ia), 1910747 (Ib), and 1910748 (Ic)). In the molecules of compounds Ia–Ic, the L1 macrocyclic ligand coordinates the metal atom by four nitrogen atoms via the tetradentate chelate mode to form the polyhedron as a distorted tetrahedron.

Crystal structure, Hirshfeld surface analysis, DFT calculations and molecular docking studies on pyridine derivatives as potential inhibitors of NAMPT

Abstract The crystal structure of 4-(4-fluorophenyl)-2-(1H-indol-3-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ia) and 2-(1H-indol-3-yl)-4-(thiophen-2-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ib) were elucidated by single crystal X ray diffraction. The central piperidine ring adopts twisted conformation, the piperidine of octahydroindolizine ring is in half chair conformation and the pyrrole ring is in twisted envelope conformation in both the compounds (Ia) and (Ib). Details of the preparation, crystal structure determination and intra- and inter- molecular interactions of the compounds are given. Intermolecular interactions were also studied by Hirshfeld surface analysis. The structures of both compounds were optimized by density functional theory (DFT) calculations using B3LYP hybrid functional with 6–311G(2d,2p)level basis set. The molecular docking study of synthesized compound with an enzyme, namely, Nicotinamidephosphoribosyltransferase (NAMPT) which increases sensitivity to apoptosis in both NAMPT-expressing cells and tumorspheres has also been carried out.

Computational design, Synthesis of 4,6-dihydroxy-2-phenyl-1-benzofuran-3(2H)-one derivatives as new leads for anti-cancer activity

Benzofuranone is a bicyclic ring where a benzene ring fused with a furanone. Computation chemistry plays a major role in the development of new lead molecules. Computational tools docking, virtual screening, ADMET prediction are utilised in the identification of new lead molecules. Synthetic chemistry plays a major in developing a series of potent anti-cancer agents. Benzofuranone was synthesized by reacting benzene diols, and triols with bromo phenyl acetonitrile yielded an imine derivative are converted to a ketone with treatment with hydrochloric acid then cyclised with sodium acetate. The compounds identity and purity were confirmed by spectral and analytical methods. Benzofuranone derivatives are screened antineoplastic activity was performed against human skin cancer cell line G361 at micro molecular concentrations. The compounds IA, IB, ID, IE, IF, was found to be with potent activity.

Synthesis, insecticidal evaluation and mode of action of novel anthranilic diamide derivatives containing sulfur moiety as potential ryanodine receptor activators.

Anthranilic diamide insecticide could control lepidopteran pests by selectively binding and activating insect ryanodine receptors (RyRs), and the unique mode of action is different from other conventional insecticides. In order to discover new anthranilic diamide insecticide as ryanodine receptors activators, a series of 11 novel anthranilic diamides derivatives (Ia-k) were synthesized and confirmed by melting point, 1H NMR, 13C NMR and elemental analyses. The preliminary bioactivity revealed that most title compounds showed moderate to remarkable activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Especially, compounds Ia and If, which exhibited 100% larvicidal activity against oriental armyworm at 1.0 mg L-1, and comparable to that of chlorantraniliprole (100% at 1 mg L-1). If displayed 60% insecticidal activity against diamondback moth at 0.01 mg L-1, better than chlorantraniliprole (45% at 0.01 mg L-1). The preliminary structure activity relationships were discussed. In addition, the calcium imaging experiment indicated that the insect ryanodine receptor is the potential target of If.

Coordination Compounds of Cobalt(II), Nickel(II), and Copper(II) Halides with 2-Methyl-1,2,4-Triazolo[1,5-a]benzimidazole

New coordination compounds of Co(II), Ni(II), and Cu(II) halides with 2-methyl-1,2,4-triazolo[1,5-a]benzimidazole (L), [Co(L)2Cl2] (Ia), [Ni(L)2(H2O)4]Cl2 · 4H2O (II), and [Сu2(L)4(µ-Br)2Br2] (IIIa), are synthesized. The complexes are studied by X-ray structure analysis (СIF files CCDC nos. 1825006–1825008), electronic (diffuse reflectance) spectroscopy, and IR spectroscopy. In compounds Ia, II, and IIIa, ligand L is coordinated to the metal by the N4 atom of the triazole fragment. The study of the cytotoxic effect of the ligand and synthesized complexes on the Hep-2 line (laryngeal cancer cells) shows a considerably higher activity of the copper(II) complex than that of the ligand.

Synthesis and antitumor activities of 3-substituted-analine derivatives: structure modifications of Tuv part of tubulysins

BackgroundTubulysins family is a kind of natural compound with potent, antitumor activity. To simplify the synthesis route and find new antitumor compounds is becoming a hotspot of research recent years.ResultsStarting from 3-nitrobenzoic acid, after 7 steps transformations, 12 new tubulysin analogues were synthesized by the conformational restraint and bioisostere principle. These structures are featuring 3-substituted analine moieties. All these compounds are new compounds, and the structures were characterized by 1H NMR, 13C NMR, and HRMS. The antitumor activities were screened by the MTT method using MDA-MB-231and MCF7 cells.ConclusionsCompound IIb exhibited certain antitumor activity with the IC50 value of 7.6 and 11.8 µM against MDA-MB-231 and MCF7 cells respectively. Compounds IIa–IIe had moderate antitumor activities suggested that the thiazole ring in the Tuv could be replaced by the phenyl ring. However, Compounds Ia–Ie lose antitumor activity dramatically suggested that the conformation of the Tuv was crucial for the tubulysin analogues to maintain the biological activity.

Design, Synthesis, Biological Evaluation and SARs of Novel N‐Substituted Sulfoximines as Potential Ryanodine Receptor Modulators

The sulfoximine group has been evaluated as a pharmacophore. Introducing the sulfoximine structure into medicinal compounds as exciting motifs has brought opportunities in drug discovery. In order to develop new ryanodine receptor (RyR) modulators, a series of phthalamides containing sulfoximine derivatives were designed, synthesized, and evaluated against oriental armyworm and diamondback moth for their insecticidal activities. These studies helped to elucidate the electronic and structural requirements around the sulfoximine motif for insecticidal activity. All new structures were synthesized and characterized by 1H NMR, 13C NMR, HRMS and bioassay and a preliminary structure − activity relationship (SAR) was discussed. The biological assessment indicated that most title compounds showed good to excellent larvicidal activities. Compounds Ia, Ie, and If gave excellent insecticidal activity against oriental armyworm, which showed 100% larvicidal activity at 0.5 mg/L. All compounds showed 100% larvicidal activity at 0.1 mg/L against diamondback moth. In particular, the larvicidal activities of Ie, If, and Ih at 0.0001 mg/L were 50%, 20%, and 40%, respectively, reaching an activity as high as that of the commercial flubendiamide (40%, 0.0001 mg/L). Therefore, Ia, Ie, If and Ih could be considered as new lead structures for the development of new ryanodine receptor (RyR) modulators.

Synthesis, insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties

Ryanodine receptors (RyRs) activator has become one class of popular insecticide because of its unique mode of action. In order to find more new RyRs activators as insecticidal agents, a series of 18 novel chiral anthranilic diamides were designed by introducing the d-alanine acid and d-serine acid esters as well as trifluoroethoxyl group into the anthranilic diamide skeleton and synthesized successfully based on anthranilic diamide and FKI-1033 structures. The structures of the title compounds Ia–i and IIa–i were confirmed by melting points, 1H NMR, 13C NMR, elemental analysis and specific optical rotation analysis. The preliminary bioassay results indicated that most of the title compounds exhibited considerable larvicidal activities against oriental armyworm at 10mg/L, especially Ib, Ie and IIh showed remarkable insecticidal activities at 0.5mg/L. The larvicidal activity against diamondback moth of Ia and IId were 80% and 90% respectively at 0.0001mg/L, which was similar to that of chlorantraniliprole. The relationship between structure and insecticidal activity was analyzed to reveal a possible co-regulated effect of the chiral amino acid ester, halogen atom or cyano group, and trifluoroethyloxyl group of the skeleton structures of the title compounds, which will provide useful information for guiding the design and discovery of new RyRs activators and insecticidal agrochemicals.

ChemInform Abstract: Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010.

AbstractThe title compounds (Ia) and (Ib) possess a novel carbocyclic skeleton, represented by an unprecedented ring system.

Self‐Assembly of Hexameric Macrocycles from PtII/Ferrocene Dimetallic Subunits – Synthesis, Characterization, Chemical Reactivity, and Oxidation Behavior

AbstractNew compounds Ia–h of the form [(Me2SO)ClPt(HR2DTO κ‐S,S Pt)] (HR2DTO = secondary dithiooxamide, with R = methyl, ethyl, n‐propyl, n‐butyl, n‐decyl, isopropyl, (R)‐1‐phenylethyl, or (S)‐2‐hydroxypropyl; κ‐S,S Pt denotes the coordination of the DTO moiety to the Pt atom) have been prepared and used to synthesize platinum(II)/ferrocene dimetallic species IIa–h of formula [(dppf)Pt(HR2DTO κ‐S,S Pt)]Cl (dppf = 1,1′‐diphosphinoferrocene). Complexes IIa–e, bearing unbranched groups on the dithiooxamide moiety (i.e., R = methyl, ethyl, n‐propyl, n‐butyl, or n‐decyl groups), self‐assemble upon standing to form unprecedented hexameric macrocycles IIIa–e. Compounds IIa–e, IIIa–e, as well as IIf–h, have been characterized by a combination of 1H, 13C, 31P NMR spectroscopy and 2D‐ROESY and diffusion‐ordered NMR spectroscopy (DOSY) experiments; the latter experiments have been used to calculate the hydrodynamic radius of IIa–e and IIIa–e, assisted by the data provided by the X‐ray crystal structure of IIh. Compounds IIIa–e are characterized by the presence of six dppf bridging units occupying the inner rim of the macrocycles and exhibit interesting properties, for example, oxidation of IIIa–e occurs around +0.40 V versus saturated calomel electrode (SCE), whereas oxidation of the type II species occurs at potentials greater than +1.0 V. Oxidation of IIIa–e is explained through a delocalized orbital extending over the six dppf subunits. The reversibility of the self‐assembly process is finally demonstrated by alternate addition of acids and bases to the type III compounds.

Design, Synthesis, and Biological Evaluation of Novel 2-(Pyridin-3-yloxy)acetamide Derivatives as Potential Anti-HIV-1 Agents.

Through a structure-based molecular hybridization and bioisosterism approach, a series of novel 2-(pyridin-3-yloxy)acetamide derivatives were designed, synthesized, and evaluated for their anti-HIV activities in MT-4 cell cultures. Biological results showed that three compounds (Ia, Ih, and Ij) exhibited moderate inhibitory activities against wild-type (wt) HIV-1 strain (IIIB ) with EC50 values ranging from 8.18 μm to 41.52 μm. Among them, Ij was the most active analogue possessing an EC50 value of 8.18 μm. To further confirm the binding target, four compounds were selected to implement an HIV-1 RT inhibitory assay. In addition, preliminary structure-activity relationship (SAR) analysis and some predicted physicochemical properties of three active compounds Ia, Ih, and Ij were discussed in detail. Molecular docking studies were also carried out to investigate the binding modes of Ij and the lead compound GW678248 in the binding pocket of RT, which provided beneficial information for further rational design of non-nucleoside reverse transcriptase inhibitors.

Synthesis and Antiplatelet Aggregation Activity Evaluation of some 2-Aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine Derivatives.

A series of novel 2-aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma using light transmission aggregometry. Among the tested derivatives, compounds Ia, Ib, IB and II16 exhibited the highest antiplatelet aggregation activity (36.75, 72.4, 62.5 and 80 µM). None of the compounds showed satisfactory activity against the aggregation induced by ADP but acceptable activities were observed against the aggregation induced by arachidonic acid. 2- aminopyrimidines were more active than 4,6- diaminopyrimidines in this respect.

Synthesis and biological activity of novel amidrazones incorporating 5-nitroimidazole, ciprofloxacin, and 7-chloro-4-piperazinylquinoline

Series of new amidrazones Ia–c, IIa–c, and IIIc, incorporating 5-nitroimidazole (a), ciprofloxacin (b), and 7-chloro-4-piperazinylquinoline (c) moieties, were synthesized by reacting hydrazonoyl chlorides I–III, derived from 4-fluoroaniline and 4-chloroaniline with the proper amine, in the presence of triethylamine. Structures of the prepared compounds were confirmed by 1H NMR, 13C NMR, and ESI-HRMS spectral data. The antitumor, antibacterial, and antiparasitic activities of the newly synthesized compounds were evaluated. Compounds Ic and IIc exhibited strong anticancer activity against all tested cancer cell lines. In addition, compounds Ia and IIa displayed stronger antimicrobial potency than metronidazole against microaerophilic bacteria. Compounds IIa, IIIc, and IIc, exhibited remarkable antigiardial activity and were found to be more active than metronidazole with IC50 of 5.6, 5.9, and 6.8 µg/mL, respectively. Compounds Ia, Ib, and Ic also exhibited antigiardial activity with similar IC50 values compared to the reference drug metronidazole (IC50 = 6.9 µg/mL). On the other hand, compounds Ia, Ib, and IIa exhibited significant antitrichomonal activity and found to be more active than metronidazole with IC50 of 3.79, 4.6, and 5.1 µg/mL, respectively, compared to the reference drug metronidazole (8.79 µg/mL).

Chiral Dicarboxamide Scaffolds Containing a Sulfiliminyl Moiety as Potential Ryanodine Receptor Activators

To search for new environmentally benign insecticides with high activity, low toxicity, and low residue, novel chiral configurations introduced into dicarboxamide scaffolds containing N-cyano sulfiliminyl moieties were first studied. Four series of phthalamides with sulfur-containing side chains were designed, synthesized, and evaluated against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)) for their insecticidal activities. All structures were characterized by (1)H NMR, (13)C NMR, and HRMS (or elemental analysis), and their configurations were confirmed by optical polarimetry. The biological assessment indicated that some title compounds exhibited significant insecticidal activities. For oriental armyworm, these stereoisomers exerted different impacts on biological activity following the sequence (Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Ss) > (Rc, Rs), and carbon chirality influenced the activities more strongly than sulfur. Compounds Ia and IIa reached as high an activity as commercial flubendiamide, with LC50 values of 0.0504 and 0.0699 mg L(-1), respectively, lower than that of flubendiamide (0.1230 mg L(-1)). For diamondback moth, the sequence of activity was (Sc, Ss) > (Sc, Rs), and the sulfur chirality influenced the activities more greatly than carbon. Compound IIe exhibited even higher activity than flubendiamide, whereas Ie and Ic,d reached the activity of the latter. The results indicated that the improvement of insecticidal activity probably required a coordination of both carbon and sulfur chirality. Comparative molecular field analysis calculation indicated that stereoisomers with Sc configurations containing strong electron-withdrawing groups such as as CN are important in maintaining the high activity. The chiral scaffolds containing the N-cyano sulfiliminyl moiety are also essential for high larvicidal activity. Some title compounds could be considered as potential candidates for ryanodine receptor activators.