Synthesis and Fungicidal Activities of New 1,2,4‐Triazolo[1,5‐a]pyrimidines

A series of new acetohydrazone‐containing 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives were designed and synthesized for the purpose of searching for novel agrochemicals with higher fungicidal activity. Their in vitro fungicidal activities against Rhizoctonia solani were evaluated, and the most promising compound, 2‐[(5,7‐dimethyl[1,2,4]triazolo[1,5‐a]pyrimidin‐2‐yl)sulfanyl]‐2′‐[(2‐hydroxyphenyl)methylidene]acetohydrazide ( 2‐17 ), showed a lower EC₅₀ value (5.34 μg ml^?1) than that of commercial carbendazim (EC₅₀=7.62 μg ml^?1). Additionally, compound 2‐17 was also found to display broad‐spectrum fungicidal activities, and its EC₅₀ value (4.56 μg ml^?1) against Botrytis cinereapers was very similar to that of carbendazim. Qualitative structure–activity relationships (QSARs) of the synthesized compounds were also discussed.     

Design,Synthesis, and Cholinesterase Inhibition Assay of Coumarin‐3‐carboxamide‐N‐morpholine Hybrids as New Anti‐Alzheimer Agents

A new series of coumarin‐3‐carboxamide‐N‐morpholine hybrids 5a – 5l was designed and synthesized as cholinesterases inhibitors. The synthetic approach for title compounds was started from the reaction between 2‐hydroxybenzaldehyde derivatives and Meldrum's acid to afford corresponding coumarin‐3‐carboxylic acids. Then, amidation of the latter compounds with 2‐morpholinoethylamine or N‐(3‐aminopropyl)morpholine led to the formation of the compounds 5a – 5l . The in vitro inhibition screen against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) revealed that most of the synthesized compounds had potent AChE inhibitory while their BuChE inhibitions are moderate to weak. Among them, propylmorpholine derivative 5g (N‐[3‐(morpholin‐4‐yl)propyl]‐2‐oxo‐2H‐chromene‐3‐carboxamide) bearing an unsubstituted coumarin moiety and ethylmorpholine derivative 5d (6‐bromo‐N‐[2‐(morpholin‐4‐yl)ethyl]‐2‐oxo‐2H‐chromene‐3‐carboxamide) bearing a 6‐bromocoumarin moiety showed the most activity against AChE and BuChE, respectively. The inhibitory activity of compound 5g against AChE was 1.78 times more than that of rivastigmine and anti‐BuChE activity of compound 5d is approximately same as rivastigmine. Kinetic and docking studies confirmed the dual binding site ability of compound 5g to inhibit AChE.     

Purification,crystal structure and antimicrobial activity of phenazine‐1‐carboxamide produced by a growth‐promoting biocontrol bacterium,Pseudomonas aeruginosa MML2212

Aim: To purify and characterize an antimicrobial compound produced by a biocontrol bacterium, Pseudomonas aeruginosa MML2212, and evaluate its activity against rice pathogens, Rhizoctonia solani and Xanthomonas oryzae pv. oryzae. Methods and Results: Pseudomonas aeruginosa strain MML2212 isolated from the rice rhizosphere with wide‐spectrum antimicrobial activity was cultured in Kings’B broth using a fermentor for 36 h. The extracellular metabolites were isolated from the fermented broth using ethyl acetate extraction and purified by two‐step silica‐gel column chromatography. Three fractions were separated, of which a major compound was obtained in pure state as yellow needles. It was crystallized after dissolving with chloroform followed by slow evaporation. It is odourless with a melting point of 220–222°C. It was soluble in most of the organic solvents and poorly soluble in water. The molecular mass of purified compound was estimated as 223·3 by mass spectral analysis. Further, it was characterized by IR, ¹H and ¹³C NMR spectral analyses. The crystal structure of the compound was elucidated for the first time by X‐ray diffraction study and deposited in the Cambridge Crystallographic Data Centre ( http://www.ccde.com.ac.uk ) with the accession no. CCDC 617344 . Conclusion: The crystal compound was undoubtedly identified as phenazine‐1‐carboxamide (PCN) with the empirical formula of C₁₃H₉N₃O. Significance and Impact of the Study: As this is the first report on the crystal structure of PCN, it provides additional information to the structural chemistry. Furthermore, the present study reports the antimicrobial activity of purified PCN on major rice pathogens, R. solani and X. oryzae pv. oryzae. Therefore, the PCN can be developed as an ideal agrochemical candidate for the control of both sheath blight and bacterial leaf blight diseases of rice.     

1‐Phenyl‐3‐pentanone,a Volatile Compound from the Edible Mushroom Mycoleptodonoides aitchisonii Active Against Some Phytopathogenic Fungi

Volatiles produced by mycelia of mushrooms with aromatic odour were investigated for their antifungal activity against plant‐pathogenic fungi. The results of the screening of 23 species of basidiomycetes revealed that volatile substances from mycelia of Mycoleptodonoides aitchisonii (TUFC10099), an edible mushroom, strongly inhibited the mycelial growth, spore germination and lesion formation on host leaves of some plant‐pathogenic fungi including Alternaria alternata, A. brassicicola, A. brassicae, Colletotrichum orbiculare and Corynespora cassiicola. The volatile compounds were isolated from the culture filtrate of M. aitchisonii, and 1‐phenyl‐3‐pentanone was identified as a major antifungal volatile. The compound had significantly inhibitory activity against plant‐pathogenic fungi at 35 ppm. This is the first report that the volatile compound produced by mycelia of M. aitchisonii has antifungal activity against plant‐pathogenic fungi.     

Modification,Biological Evaluation and SAR Studies of Novel 1H‐Pyrazol Derivatives Containing N,N′‐Disubstituted Urea Moiety as Potential Anti‐melanoma Agents

Malignant melanomas are amongst the most aggressive cancers. BRAF Inhibitors have exhibited therapeutic effects against BRAF‐mutant melanoma. In continuation of our earlier studies on anti‐melanoma agents based on 1H‐pyrazole skeleton, two sets of novel compounds that include 1H‐pyrazole‐4‐amines FA 1 – FA13 and corresponding urea derivatives FN 1 – FN13 have been synthesized and evaluated for their BRAF^V600E inhibitory and antiproliferation activities. Compound FN 10 displayed the most potent biological activity against BRAF^V600E (IC₅₀ = 0.066 μm ) and the A375 human melanoma cell line (GI₅₀ = 0.81 μm ), which was comparable to the positive control vemurafenib, and more potent than our previously reported 1H‐pyrazole‐3‐amines and their urea derivatives. The results of SAR studies and molecular docking can guide further optimization and may help to improve potency of these pyrazole‐based anti‐melanoma agents.     

Synthesis and Antifungal Activity of 2‐Hydroxy‐4,5‐methylenedioxyaryl Ketones as Analogues of Kakuol

In a study aiming to determine the structural elements essential to the antifungal activity of kakuol, we synthesized a series of 2‐hydroxy‐4,5‐methylenedioxyaryl ketones, and we assayed their in vitro antifungal activity. The most sensitive target organisms to the action of these class of compounds were Phytophthora infestans, Phytium ultimum, Cercospora beticola, Cladosporium cucumerinum, and Rhizoctonia solani. Most of the analogs showed a remarkable in vitro activity, and some of them appeared significantly more effective than the natural product. The biological activity was mainly affected by introducing structural modification on the carbonyl moiety of the natural‐product molecule. In particular, compound 5a , bearing a C?C bond conjugated to the C?O group, was found active with a MIC value of 10 μg ml^?1 against Cladosporium cucumerinum. The results suggest that 2‐hydroxy‐4,5‐methylenedioxyaryl ketones can be considered promising candidates in the development of new antifungal compounds.     

Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine]

It was shown that racemic (±)‐ 2 [1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine], WMS‐1813 ] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ₁ receptors. To study the pharmacological activity of the enantiomers of 2 , a preparative HPLC separation of (R)‐2 and (S)‐2 was performed. The absolute configuration of the enantiomers was determined by CD‐spectroscopy together with theoretical calculations of the CD‐spectrum of a model compound. In receptor binding studies with the radioligand [³H]‐(+)‐pentazocine, (S)‐2 was thrice more potent than its (R)‐configured enantiomer (R)‐2 . The metabolic degradation of the more potent (S)‐enantiomer was considerably slower than the metabolism of (R)‐2 . The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap‐LC‐MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2 . Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Synthesis,Antimicrobial Activity and Molecular Docking Study of Novel α‐(Diphenylphosphoryl)‐ and α‐(Diphenylphosphorothioyl)cycloalkanone Oximes

A series of novel α‐(diphenylphosphoryl)‐ and α‐(diphenylphosphorothioyl)cycloalkanone oximes have been synthesized in search for novel bioactive molecules. Their structures were characterized by various spectroscopic methods including IR, NMR (¹H, ³¹P, ¹³C), mass spectrometry and single crystal X‐ray diffraction. The newly synthesized phosphorus‐containing oximes were screened for their in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium) and fungal strains (Candida albicans and Candida glabrata). The biological assays showed that all the studied compounds exhibited high antibacterial and antifungal activities at only 0.1–2.1 μg/mL. In silico molecular docking studies in FabH enzyme active site were performed in order to predict the possible interaction modes and binding energies of the drug candidates at the molecular level.     

Synthesis,photoluminescence properties and theoretical insights on 1,3‐diphenyl‐5‐(9‐anthryl)‐2‐pyrazoline and ‐1H‐pyrazole

1,3‐Diphenyl‐5‐(9‐anthryl)‐2‐pyrazoline and 1,3‐diphenyl‐5‐(9‐anthryl)‐1H‐pyrazole with an anthryl chromophore were synthesized and characterized using ¹H NMR, ¹³C NMR, FT‐IR, mass spectrometry and elemental analysis. Their optical properties were characterized by UV–vis absorption and fluorescence spectroscopy. It was observed that the absorption and fluorescence spectra of the two compounds showed a red shift with respect to that of anthracene. Pyrazole exhibited high fluorescent quantum yields (Φ_f = 0.90 in toluene) while pyrazoline showed nearly no fluorescence in solution. The significant fluorescence divergence of the two similar compounds was investigated theoretically through density functional theory (DFT) calculations. The energetically lowest‐lying state S₁ in the pyrazoline exhibited both characteristics of locally excited and electron‐transfer states that resulted in the fluorescence quenching of anthryl chromophore whereas the S₁ state in the pyrazole corresponded to an optically allowed state that led to high fluorescence quantum yields in solutions. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis and Antifungal Activities of Trichodermin Derivatives as Fungicides on Rice

Twenty new trichodermin derivatives, 2a – 5 , containing alkoxy, acyloxy, and Br groups in 4‐, 8‐, 9‐, 10‐ and 16‐positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4‐, 8‐, and 16‐positions, but low to changes at 9‐ and 10‐positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50 mg l^?1. Compound 4 (9‐formyltrichodermin; EC₅₀ 0.80 mg l^?1) with an CHO group at 9‐position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC₅₀ 0.82 mg l^?1), while compound 3f ((8R)‐8‐{[(E)‐3‐phenylprop‐2‐enoyl]oxy}trichodermin; EC₅₀ 3.58 and 0.74 mg l^?1) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC₅₀ 0.96 mg l^?1) and propiconazole (EC₅₀ 5.92 mg l^?1), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future.     

Molecular Insight and Mode of Inhibition of α‐Glucosidase and α‐Amylase by Pahangensin A from Alpinia pahangensis Ridl.

The inhibition of carbohydrate‐hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A ( 1 ), a bis‐labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl ., was identified as an active dual inhibitor for α‐amylase (IC₅₀=114.80 μm ) and α‐glucosidase (IC₅₀=153.87 μm ). This is the first report on the dual α‐amylase and α‐glucosidase inhibitory activities of a bis‐labdanic diterpene. The Lineweaver‐Burk plots of compound 1 indicate that it is a mixed‐type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non‐active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.     

Design,Synthesis, and Antifungal Activities of Novel Carboxamides Derivatives Bearing a Chalcone Scaffold as Potential SDHIs

In search for SDHIs fungicides, twenty-five novel carboxamides containing a chalcone scaffold were designed, synthesized, and evaluated for antifungal activities against five pathogenic fungi. The results showed that compound 5 k exhibited outstanding antifungal activity against R. solani with an EC₅₀ value of 0.20 μg/mL, which was much better than that of commercial SDHIs Boscalid (EC₅₀=0.74 μg/mL). Moreover, compound 5 k also displayed promising antifungal activities against S. sclerotiorum, B. cinerea, and A. alternate (IC₅₀=2.53–4.06 μg/mL), indicating that 5 k had broad-spectrum antifungal activity. Additionally, in vivo antifungal activities results showed that 5 k could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (57.78 %) and curative efficacy (58.45 %) at 100 μg/mL, both of which were much better than those of Boscalid, indicating a promising application prospect. Moreover, SEM analysis showed that compound 5 k could remarkably disrupt the typical structure and morphology of R. solani hyphae. Further SDH enzyme inhibition assay and molecular docking study revealed that lead compound 5 k had a similar mechanism of action as commercial SDHI Boscalid. These results indicated that compound 5 k showed potential as a SDHIs fungicide and deserved further investigation.     

BIOSYNTHESIS OF POLY‐3‐HYDROXYBUTYRATE (PHB) IN THE TRANSGENIC GREEN ALGA CHLAMYDOMONAS REINHARDTII1

A cell‐wall deficient strain of Chlamydomonas reinhardtii P. A Dang. CC‐849 was cotransformed with two expression vectors, p105B124 and pH105C124, containing phbB and phbC genes, respectively, from Ralstonia eutropha. The transformants were selected on Tris‐acetate‐phosphate media containing 10 μg · mL^?1 Zeomycin. Upon further screening, the transgenic algae were subcloned and maintained in culture. PCR analysis demonstrated that both phbB and phbC genes were successfully integrated into the algal nuclear genome. Poly‐3‐hydroxybutyrate (PHB) synthase activity in these transgenic algae ranged from 5.4 nmol · min^?1 · mg protein^?1 to 126 nmol · min^?1 · mg protein^?1. The amount of PHB in double transgenic algae was determined by gas chromatography–mass spectrometry (GC–MS) when comparing with PHB standard. In addition, PHB granules were observed in the cytoplasm of transgenic algal cells using TEM, which indicated that PHB was synthesized in transgenic C. reinhardtii. Hence, results clearly showed that producing PHB in C. reinhardtii was feasible. Further studies would focus on enhancing PHB production in the transgenic algae and targeting the chloroplast for PHB accumulation.     

Identification of a naturally‐occurring 8‐[α‐D‐glucopyranosyl‐(1→6)‐β‐D‐glucopyranosyl]daidzein from cultivated kudzu root

Introduction – Kudzu root (Radix puerariae) is a rich source of isoflavones that are effective in preventing osteoporosis, heart disease and symptoms associated with menopause. The major isoflavonoids in kudzu root extracts were reported as puerarin, daidzin and daidzein. Recently, an unknown isoflavonoid (compound 1) was detected from one‐year‐old kudzu root cultivated in Vietnam. Objective – To identify a novel compound 1 in kudzu root extract and determine the structure of the compound by ESI⁺ TOF MS‐MS, ¹H‐, ¹³C‐NMR and enzymatic hydrolysis. Methodology – Samples were prepared by extraction of one‐year‐old kudzu root with 50% ethanol and the isoflavonoids were purified using recycling preparative HPLC. Unknown compound 1 was detected using UV‐light at 254 nm in TLC and HPLC analyses. The molecular weight of 1 was determined using a TOF mass spectrometer equipped with an electrospray ion source. The structure of 1 was determined from the ¹³C and ¹H NMR spectra recorded at 100.40 and 400.0 MHz, respectively. Results – ESI⁺ TOF MS‐MS analysis shows that 1 is a puerarin diglycoside. The interglycosidic linkage of diglycoside determined by ¹H‐, ¹³C‐NMR, and enzymatic hydrolysis suggests that 1 has a glucosyl residue linked to puerarin by an α‐1,6‐glycosidic bond. This compound is the first naturally‐occurring 8‐[α‐D ‐glucopyranosyl‐(1→6)‐β‐D ‐glucopyranosyl]daidzein in kudzu root. The concentration of glucosyl‐α‐1,6‐puerarin in kudzu root was 2.3 mg/g as determined by HPLC. Conclusion – The results indicate that puerarin diglycoside is one of the major isoflavonoids in kudzu root and has a significant impact on the preparation of highly water‐soluble glycosylated puerarin. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis,Antifungal Activity,DFT Study and Molecular Dynamics Simulation of Novel 4-(1,2,4-Oxadiazol-3-yl)-N-(4-phenoxyphenyl)benzamide Derivatives

In order to find novel potential antifungal agrochemicals, a series of new 4-(1,2,4-oxadiazol-3-yl)-N-(4-phenoxyphenyl)benzamide derivatives 3a – j were designed, synthesized and characterized by their ¹H - , ¹³C-NMR and HRMS spectra. The preliminary antifungal assay in vitro revealed that compounds 3a – j exhibited moderate to good antifungal activity against five plant pathogenic fungi. Especially, compound 3e presented significant antifungal activity against Alternaria solani, Botrytis cinerea and Sclerotinia sclerotiorum, superior to positive control boscalid. In the in vivo antifungal assay on tomato plants and cucumber leaves, compound 3e presented good inhibition rate against B. cinerea at 200 mg/L. Molecular dynamics simulation revealed that compound 3e could bind with the active site of class II histone deacetylase (HDAC).     

Design and Synthesis of Novel Arylisoxazole‐Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease

A novel series of hybrid arylisoxazole‐chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase (ChE) inhibitory activity based on the modified Ellman's method. Among synthesized compounds, 5‐(3‐nitrophenyl)‐N‐{4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide depicted the most acetylcholinesterase (AChE) inhibitory activity (IC₅₀=1.23 μm ) and 5‐(3‐chlorophenyl)‐N‐{4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide was found to be the most potent butyrylcholinesterase (BChE) inhibitor (IC₅₀=9.71 μm ). 5‐(3‐Nitrophenyl)‐N‐{4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide was further investigated for its BACE1 inhibitory activity as well as neuroprotectivity and metal chelating ability as important factors involved in onset and progress of Alzheimer's disease. It could inhibit BACE1 by 48.46 % at 50 μm . It also showed 6.4 % protection at 25 μm and satisfactory chelating ability toward Zn²⁺, Fe²⁺, and Cu²⁺ ions. Docking studies of 5‐(3‐nitrophenyl)‐N‐{4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide and 5‐(3‐chlorophenyl)‐N‐{4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide confirmed desired interactions with those amino acid residues of the AChE and BChE, respectively.     

Natural Product‐Based Fungicides Discovery: Design,Synthesis and Antifungal Activities of Some Sarisan Analogs Containing 1,3,4‐Oxadiazole Moieties

A series of sarisan analogs containing 1,3,4‐oxadiazole moieties were synthesized by iodine‐mediated oxidative cyclization and screened in vitro for their antifungal activities at 50 μg/mL against five phytopathogenic fungi such as Valsa mali, Curvularia lunata, Alternaria alternate, Fusarium solani and Fusarium graminearum. 1,3,4‐Oxadiazole derivatives 7e , 7p , 7r , 7t and 7u exhibited potent and a broad spectrum of antifungal activities against at least three phytopathogenic fungi at the concentration of 50 μg/mL. Especially, compound 7r displayed more potent antifungal activities against five phytopathogenic fungi than the positive control hymexazol. The EC₅₀ of 7r against V. mali, C. lunata and A. alternate were 12.6, 14.5 and 17.0 μg/mL, respectively. Additionally, some interesting results of structure‐activity relationships (SARs) were also observed.     

Antimycotic activities of Cinnamon-derived compounds against <Emphasis Type="Italic">Rhizoctonia solani</Emphasis> in vitro

In this study, the effects of medicinal plant extracts on the development of mycelium in the following phytopathogenic fungi were evaluated: Phytophthora capsici, Rhizoctonia solani, Fusarium solani, Colletotrichum gloeosprorioides, and Botrytis cinera. Of the 26 medicinal plants tested, six plant extracts showed antifungal activity against phytopathogenic fungi. The highest antifungal activity was exerted against R. solani by the n-hexane fraction of a Cinnamon (Cinnamomum cassia Blume) solvent extract. Therefore, the antifungal compound fractions I and II were purified from the n-hexane fraction by TLC on silica gel plates. When treated with solutions containing compound fractions I or II at a concentration of 2%, the mycelia growth rate of R. solani was reduced to 0.19 and 0.18, respectively. In addition, microscopic observation of the hyphal morphology of R. solani following treatment with compound fraction I revealed the presence of severely damaged hyphae. Specifically, the hyphal tips became swollen, collapsed or were completely destroyed in response to treatment with solution containing compound fraction I at concentration of 1%.     

A Highly Enantioselective Access to Chiral 1‐(β‐Arylalkyl)‐1H‐1,2,4‐triazole Derivatives as Potential Agricultural Bactericides

A series of chiral 1‐(β‐arylalkyl)‐1H‐1,2,4‐triazole derivatives has been designed as potential antifungal agents. The target triazoles have been synthesized by using a chiral auxiliary as a controlling reagent. All of the compounds were obtained with high ee values, reaching up to 99%. Preliminary bioassay results have revealed that most of the synthesized compounds display significantly higher fungicidal activities against the species Fusarium oxysporium, Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii than the commercial agent triadimefon. Moreover, some of the enantiomers have been found to display significant differences in activity.     

Synthesis and in Vitro Antimicrobial Activity Screening of New 3‐Acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline Derivatives

Thirteen new 3‐acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline derivatives were synthesized from corresponding hydrazide‐hydrazones of isonicotinic acid in the reaction with acetic anhydride. The obtained compounds were identified with the use of spectral methods (IR, ¹H‐NMR, ¹³C‐NMR, MS). In vitro antimicrobial activity screening of synthesized compounds against a panel of bacteria and fungi revealed interesting antibacterial and antifungal activity of tested 1,3,4‐oxadiazoline derivatives, which is comparable to that of commonly used antimicrobial agents.