Semisynthesis and biological evaluation of novel honokiol thioethers against colon cancer cells HCT116 via inhibiting the transcription and expression of YAP protein.

Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC50 value of 6.1 µmol/L, superior to the reference drug 5-fluorouracil (IC50: 9.63 ± 0.27 µmol/L). The structure-activity relationships (SARs) indicated that the introduction of -(4-NO2)Ph, 3-pyridyl, -(2-F)Ph, -(4-F)Ph, -(3-F)Ph, -(4-Cl)Ph, and -(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.

Novel 1,3,4-oxadiazole hybrids of 3-n-butylphthalide derivatives as potential anti-ischemic stroke agents.

In continuation of our program to search for novel potential anti-ischemic stroke agents, a series of 1,3,4-oxadiazole and sulfoxide hybrids of phthalide derivatives was designed and synthesized in this study to evaluate their anti-ischemic stroke activity. Among them, compounds 5b, 5d, 5 l, and 5 m exhibited excellent inhibitory effects on platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA). In particular, compound 5b possessed considerable antithrombotic activity in animal models, as demonstrated by the effective alleviation of carrageenan-induced and FeCl3-induced thrombosis in tail and carotid arteries, respectively. Notably, intraperitoneal administration of compound 5b could better protect the brain from injury caused by ischemia/reperfusion in rats compared with precursor 3-n-butylphthalide. Further pharmacokinetics, liver microsomal stability, and PAMPA-BBB assays also indicated that compound 5b had relatively high bioavailability, metabolic stability, and BBB permeability. Moreover, compound 5b showed a safety profile that was superior to the clinical drugs clopidogrel, aspirin, and 3-n-butylphthalide in the mouse-tail bleeding assay. Finally, molecular docking predicted that the potential target of the antiplatelet aggregation activity of compound 5b was P2Y12 receptor. This research provides a novel candidate compound for the treatment of ischemic stroke.

New daphnane diterpenoidal 1,3,4-oxdiazole derivatives as potential anti-hepatoma agents: Synthesis, biological evaluation and molecular modeling studies.

Hepatocellular carcinoma (HCC) is a major challenge for human healthy. Daphnane-type diterpenes have attracted increasingly attention due to remarkable pharmaceutical potential including anti-HCC activity. To further develop this class of compounds as inhibitors of HCC, the daphnane diterpenoids 12-O-debenzoyl-Yuanhuacine (YHC) and 12-hydroxydaphnetoxin (YHE) were prepared by a standard chemical transformation from dried flower buds of the Daphne genkwa plant. Subsequently, 22 daphnane diterpenoidal 1,3,4-oxdiazole derivatives were rationally designed and synthesized based on YHC and YHE. The assessment of the target compound's anti-hepatocellular carcinoma activity revealed that YHC1 exhibited comparable activity to sorafenib in the Hep3B cell line, while demonstrating higher selectivity. The mechanistic investigation demonstrates that compound YHC1 induces cell cycle arrest at the G0/G1 phase, cellular senescence, apoptosis, and elevates cellular reactive oxygen species levels. Moreover, molecular docking and CETSA results confirm the interaction between YHC1 and YAP1 as well as TEAD1. Co-IP experiments further validated that YHC1 can effectively inhibit the binding of YAP1 and TEAD1. In conclusion, YHC1 selectively targets YAP1 and TEAD1, exhibiting its anti-hepatocellular carcinoma effects through the inhibition of their interaction.

New thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids: Synthesis, MCF-7 inhibition and binding studies.

Two synthetic methods were proposed for the preparation of a new series of thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids (TOT-1 to 15) and their structures were elucidated based on spectral data. Studies on cytotoxicity, ROS, cellular uptake and interactions of TOT-14 with calf thymus DNA were carried out. Anticancer activity of compounds, TOT-1 to 15 on breast cancer (MCF-7) cell lines was investigated. The IC50 values for the standard, epirubicin hydrochloride and TOT-12, 13, 14 and 15 were found to be 6.78, 5.52, 6.53, 4.83 and 5.57 µg/mL, respectively. Notably, TOT-14 exhibited a remarkable antiproliferative activity with a strikingly selective inhibitory effect compared to standard. This specific selectivity could be attributed to the synergistic effect of increased cellular uptake and generation of higher ROS in cancer cells after irradiation. The binding constant of 4.25 x 103 M-1 indicated the moderate interaction between TOT-14 and ct-DNA. The docking score of TOT derivativeswas substantially identical to the docking score of epirubicin hydrochloride. The designed molecules complied with the requirements for drug-likeness and ADME.

Rational design, synthesis, and antimicrobial evaluation of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety.

In this paper, a series of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety were constructed. The synthetic compounds were characterized by 1H NMR, 13C NMR, HRMS, and single crystal diffraction. The antimicrobial activities of title compounds against fungi (Pyricutaria oryzae Cav., Phomopsis sp., Botryosphaeria dothidea, cucumber Botrytis cinerea, tobacco Botrytis cinerea, blueberry Botrytis cinerea) and bacteria (Xanthomonas oryzae pv. oryzicola, Xoc; Xanthomonas axonopodis pv. citri, Xac) revealed these compounds possessed excellent antibacterial activity through mycelial growth rate method and turbidity method, respectively. Among them, compounds 7a, 7d, 7g, 7k, 7l, and 7n had the antibacterial inhibition rate of 90.68, 97.86, 93.61, 97.70, 97.26, and 92.34%, respectively. The EC50 values of 7a, 7d, 7g, 7k, 7l, and 7n were 58.31, 48.76, 58.50, 40.11, 38.15, and 46.99 µg/mL, separately, superior to that of positive control pesticide thiodiazole copper (104.26 µg/mL). The molecular docking simulation of compound 7l and glutathione s-transferase also confirmed its good activity. The in vivo bioassay toward Xac infected citrus leaves was also performed to evaluate the potential of compounds as efficient antibacterial reagent. Further study of antibacterial mechanism was also carried out, including extracellular polysaccharide production, permeability of bacterial membrane, and scanning electron microscope observations. The excellent antibacterial activities of these compounds provided a strong support for its application for preventing and control plant diseases.

Synthesis, biological activities and mechanism studies of 1,3,4-oxadiazole analogues of petiolide A as anticancer agents.

In order to develop new natural product-based anticancer agents, a series of 1,3,4-oxadiazole analogues based on petiolide A were prepared and evaluated for their anticancer activities by MTT method. The structures of all analogues were characterized by various spectral analyses, and B9 was further confirmed by X-ray crystallography. Among all the synthesized compounds, B1 displayed the most promising growth inhibitory effect on colon cancer cells (HCT116) with the IC50 value of 8.53 µM. Flow cytometric analysis exhibited that B1 arrested the cell cycle at G2 phase and induced apoptosis. Additionally, network pharmacology analysis calculated that B1 might target several key proteins, including AKT serine/threonine kinase 1 (AKT1), SRC proto-oncogene, non-receptor tyrosine kinase (SRC) and epidermal growth factor receptor (EGFR). Furthermore, molecular docking study indicated that B1 had potentially high binding affinity to these three target proteins. Given these results, analogue B1 could be deeply developed as potential anticancer agents.

Towards new bioactive fluorine-containing 1,3,4-oxadiazole-amide derivatives: synthesis, antibacterial activity, molecular docking and molecular dynamics simulation study.

Through the approach of molecular hybridization, this study rationally designed and synthesized new trifluoromethyl-1,3,4-oxadiazole amide derivatives, denoted as 1a-1n. The findings reveal that these novel molecules exhibit potent inhibitory effects against various bacterial strains. Thereinto, compounds 1c, 1d, 1i, 1j and 1n, demonstrate relatively superior antimicrobial performance against B. cereus FM314, with a minimum inhibitory concentration (MIC) of 0.03907 µg/mL. Molecular docking analysis suggests the potential importance of the Ser57 and Thr125 amino acid residues (PDB ID: 4EI9) in contributing to the inhibitory activity against B. cereus. The consistency of these results was further corroborated through subsequent molecular dynamics simulations and MMPBSA validations. The insights gained from this study serve to facilitate the rational design and efficient development of novel eco-friendly antimicrobial inhibitors based on the trifluoromethyl-1,3,4-oxadiazole amide scaffold.

Novel quinolone substituted 1,3,4-oxadiazole derivatives: design, synthesis, antimicrobial and anti-inflammatory potential.

A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using (Candida albicans, ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. IR, 1H NMR and Mass spectrometry techniques confirmed the structure of synthesized derivatives. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed significant antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds 4(a-l) did not respond well against Candida albicans fungal strain. The compound (4k) represents high % inhibition against COX-II. The compounds (4f, 4h and 4k) exhibited highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of - 8.4, - 8.6 and - 8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.

"Antibacterial effect and possible mechanism of action of 1,3,4-oxadiazole in Staphylococcus aureus".

Staphylococcus aureus is one of the main etiological agents causing foodborne diseases, and the development of new antibacterial agents is urgent. This study evaluated the antibacterial activity and the possible mechanism of action of the 1,3,4-oxadiazole LMM6 against S. aureus. The minimum inhibitory concentration (MIC) of LMM6 ranged from 1.95 to 7.81 µg ml-1. The time-kill assay showed that 48-h treatment at 1× to 8× MIC reduced S. aureus by 4 log colony forming unit (CFU), indicating a bacteriostatic effect. Regarding the possible mechanism of action of LMM6, there was accumulation of reactive oxygen species (ROS) and an increase in the absorption of crystal violet (∼50%) by the cells treated with LMM6 at 1× and 2× MIC for 6-12 h. In addition, there was increased propidium iodide uptake (∼84%) after exposure to LMM6 for 12 h at 2× MIC. After 48 h of treatment, 100% of bacteria had been injured. Scanning electron microscopy observations demonstrated that LMM6-treated cells were smaller compared with the untreated group. LMM6 exhibited bacteriostatic activity and its mechanism of action involves increase of intracellular ROS and disturbance of the cell membrane, which can be considered a key target for controlling the growth of S. aureus.

Syntheses and Cytotoxicities of Quinazolinone-Based Conjugates.

Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a-l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a-e), were designed and synthesized and their cytotoxic activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7 cell lines, while 8b-d with the thioether-linked benzimidazole moiety incorporated on the right side of the oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead compounds that merit further optimization and development as anti-cancer agents.

Design and Synthesis of Novel Phthalide Derivatives containing 1,3,4-Oxadiazole/1,2,4-Triazole Units as Potential Antifungal Agents.

Four series of novel 1,3,4-oxadiazole/1,2,4-triazole hybrids of phthalide derivatives were designed and synthesized to search for novel potential antifungal agents. Preliminary antifungal activity assay results showed that compounds 4 a, 4 b, 4 m, 5 b, 5 f, 5 h, and 7 h exhibited moderate to excellent inhibitory activity against some phytopathogenic fungi. Among them, compound 5 b displayed the most outstanding antifungal effects against V. mali and S. sclerotiorum, with the EC50 mean of 3.96 µg/mL and 5.60 µg/mL, respectively, which was superior to those of commercial fungicides hymexazol and chlorothalonil. Furthermore, compound 5 b could completely suppress the spore germination of V. mali at a concentration of 10 µg/mL. Finally, molecular docking revealed that the potential target for the antifungal activity of compound 5 b was succinate dehydrogenase (SDH). This research provides novel candidate compounds for the prevention of phytopathogenic fungi.

Design, Synthesis of Flurbiprofen Based 1,3,4-Oxadiazoles and Constrained Anticancer, Antioxidant Agents: In silico Docking Analysis.

Flurbiprofen, a primary component of a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis, and is a considerable interest in medicinal chemistry due to its demonstrated potential as an effective agent in various therapeutic applications. The synthesized series (6a-k) was characterized using a combination of spectroscopic techniques, including FT-IR, mass, 1H NMR, and 13C NMR, physical data. In the series, analogues 6c, 6e, 6h, and 6k showed excellent inhibitory activity against MCF-7 cells in the range of IC50 values of 9.10 to 13.67 µg. mL-1 compared to DXN (IC50 = 9.24 µg. mL-1). In this series, analogues 6c, 6f, 6h, and 6j show remarkable H2O2 radical scavenging inhibition IC50 of 48.25 ± 0.21, 47.33 ± 0.15, 51.10 ± 0.25, and 44.40 ± 0.07 µM by using ascorbic acid as a standard, whose IC50 is 49.90 ± 0.27 µM. According to the docking results, the most potent cytotoxic compounds have a stronger binding affinity with the Flurbiprofen complex (PDB: 1R9O) because of their interactions with residues such as Arg416(A), Trp103(A), Phe97(A), Gly279(A), Ile188(A), Glu283(A), Thr287(A), Val462(A), Phe459(A), Leu345(A), Ile417(A), and Cys418(A). Furthermore, in silico drug-likeness prediction analysis suggested that the majority of the synthesized compounds exhibit good oral bioavailability.

Eco-friendly approaches to 1,3,4-oxadiazole derivatives: A comprehensive review of green synthetic strategies.

This review article offers an environmentally benign synthesis of 1,3,4-oxadiazole derivatives, with a focus on sustainable methodologies that have minimal impact on the environment. These derivatives, known for their diverse applications, have conventionally been associated with synthesis methods that utilize hazardous reagents and produce significant waste, thereby raising environmental concerns. The green synthesis of 1,3,4-oxadiazole derivatives employs renewable substrates, nontoxic catalysts, and mild reaction conditions, aiming to minimize the environmental impact. Innovative techniques such as catalyst-based, catalyst-free, electrochemical synthesis, green-solvent-mediated synthesis, grinding, microwave-mediated synthesis, and photosynthesis are implemented, providing benefits in terms of scalability, cost-effectiveness, and ease of purification. This review emphasizes the significance of sustainable methodologies in the synthesis of 1,3,4-oxadiazole and boots for continued exploration in this research domain.

New paracetamol hybrids as anticancer and COX-2 inhibitors: Synthesis, biological evaluation and docking studies.

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC50 ) values ranging from 1.51 to 6.31 µM and anti-COX-2 activity with IC50 = 0.29 µM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy.

Design and synthesis of phenoxy methyl-oxadiazole compounds against Alzheimer's disease.

This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti-Alzheimer's agents that occur via cholinesterase and ß-secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC50 values of 0.120, 0.039, and 0.063 µM, respectively. However, the compounds showed limited effectiveness against BChE, with only a few compounds exhibiting moderate inhibition. Compound 7e showed an inhibitory effect against BACE-1 close to that of the standard drug. Structural analysis revealed that the compounds with substituted benzothiazole and thiazole moieties exhibited the most promising inhibitory activity. This study provides valuable insights into the potential of these synthesized derivatives as a treatment against Alzheimer's disease. Moreover, the structure, stability, and properties of the active compounds were further investigated using density functional theory calculations. As a final note, the utilization of molecular docking and molecular dynamics simulation studies allowed us to elucidate the action mechanism of the active compounds and gain insights into the structure-activity relationship against AChE and ß-secretase proteins. These computational techniques provide valuable information on the binding modes, interactions with target enzymes, dynamic behavior, and conformational changes of the compounds, enabling a comprehensive understanding of their biological activity.

Development of natural perfume as potential fungicide candidates: construction and biological evaluation of vanillin analogs bearing the 1,3,4-oxadiazole/1,3-thiazolidin-4-one fragments.

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 µg/ml) and 7a (38.15 µg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 µg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 µg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3-phenoxybenzoic acid as VEGFR-2 inhibitors.

Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Three compounds (4b, 4c, and 4d) exhibited cytotoxicity against two of the three cell lines tested, five compounds (3, 4a, 5a, 5b, and 5e) were toxic to one cell line, while two compounds (5c and 5d) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR-2) kinase activity data, Compound 4d was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound 4d arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound 4d has shown promising results for future research as a potent VEGFR-2 tyrosine kinase inhibitor.

Synthesis and Antitumor Activity Evaluation of Novel Echinatin Derivatives with a 1,3,4-Oxadiazole Moiety.

A series of novel echinatin derivatives with 1,3,4-oxadiazole moieties were designed and synthesized. Most of the newly synthesized compounds exhibited moderate antiproliferative activity against the four cancer cell lines. Notably, Compound T4 demonstrated the most potent activity, with IC50 values ranging from 1.71 µM to 8.60 µM against the four cancer cell lines. Cell colony formation and wound healing assays demonstrated that T4 significantly inhibited cell proliferation and inhibited migration. We discovered that T4 exhibited moderate binding affinity with the c-KIT protein through reverse docking. The results were effectively validated through subsequent molecular docking and c-KIT enzyme activity assays. In addition, Western blot analysis revealed that T4 inhibits the phosphorylation of downstream proteins of c-KIT. The results provide valuable inspiration for exploring novel insights into the design of echinatin-related hybrids as well as their potential application as c-KIT inhibitors to enhance the efficacy of candidates.

Mechanistic and Structural Insights on Difluoromethyl-1,3,4-oxadiazole Inhibitors of HDAC6.

Histone deacetylase 6 (HDAC6) is increasingly recognized for its potential in targeted disease therapy. This study delves into the mechanistic and structural nuances of HDAC6 inhibition by difluoromethyl-1,3,4-oxadiazole (DFMO) derivatives, a class of non-hydroxamic inhibitors with remarkable selectivity and potency. Employing a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) kinetic experiments, comprehensive enzymatic characterizations, and X-ray crystallography, we dissect the intricate details of the DFMO-HDAC6 interaction dynamics. More specifically, we find that the chemical structure of a DMFO and the binding mode of its difluoroacetylhydrazide derivative are crucial in determining the predominant hydrolysis mechanism. Our findings provide additional insights into two different mechanisms of DFMO hydrolysis, thus contributing to a better understanding of the HDAC6 inhibition by oxadiazoles in disease modulation and therapeutic intervention.

Synthesis and Characterization of Novel 2-Alkyl-1,3,4-Oxadiazoles Containing a Phenylazo Group.

An efficient method for the synthesis of novel phenylazo-containing moieties is described. The derivatives of 5-(4-(phenyldiazenyl)phenyl)-1,3,4-oxadiazole, substituted at position 2 of the heterocyclic scaffold with alkyl groups of different chain lengths, were prepared. The titled compounds were obtained using the appropriate 4-(5-alkyl-1,3,4-oxadiazol-2-yl)anilines, which were directed to diazotization and subsequently coupled to phenol, resorcinol, and N,N-dimethylaniline. Additionally, we report a mild and effective procedure for the preparation of 4-(5-alkyl-1,3,4-oxadiazol-2-yl)anilines via the selective reduction of the corresponding 2-alkyl-5-(4-nitrophenyl)-1,3,4-oxadiazoles using sodium borohydride-tin(II) chloride dihydrate as the reducing system. The chemical structures of the prepared compounds were confirmed by 1H- and 13C-NMR, IR, and UV-Vis spectroscopy.