Azole Derivatives Research Articles

Azole Derivatives: Cutting‐Edge Agents in Cancer Therapy

AbstractMonocyclic 5‐membered heterocycles including imidazoles, thiazoles, oxazoles, and their related compounds have gained significant attention in medicinal chemistry because of their potent anticancerous activity. These small heterocyclic molecules possess versatile properties, including biological activity, absorption, distribution, metabolism, excretion, and chemical diversity that give them immense potential as anticancer agents. It is also a fact that inherent characteristic of azoles to combine with many biological molecules through hydrogen bond, stacking, and hydrophobic interaction makes them effective against almost all cancer types. In the present paper the author discusses the way which is connected with chemical structure of monocyclic azoles and their anticancer activity namely the ability of these compounds to intercalate with DNA, to inhibit some enzymes and to interfere cellular signaling pathways. Interestingly, several azole derivatives have been seen to be effective in preclinical efficacy studies as well as in clinical trials and are considered to be potent in overcoming the problem of resistance and side effects of the common anticancer agents. As the synthetic chemistry progresses, the structural system of the azoles has diversified and development in the pharmacology has become more specific. This has helped in enhancing the formation of new molecules in the azole class with improved selectivity and efficacy. Furthermore, the comprehensive review explains how computational chemistry and structure‐activity relationship (SAR) approaches are applied to the design of future‐generation azole compounds. In light of these facts, this article is designed to give a broad overview of the current state of monocyclic azole‐based anticancer agents in an attempt to further assert its therapeutic promise and spur further attempts at infusing the said agents into the cancer therapeutics fray. The discoveries made in this study may allow the development the radical different therapeutic approaches, which could lead to improved and targeted treatment of cancer.

Synthesis and Biological Evaluation of New Chalcogen Semicarbazone (S, Se) and Their Azole Derivatives against Chagas Disease.

Chagas disease is caused by the eukaryote parasite Trypanosoma cruzi. Current treatment exhibits limited efficacy and selenium-based compounds emerged as promising candidates for new therapies which is surpassing its bioisoster, sulfur. We designed new thiosemicarbazones, thiazoles, selenosemicarbazones and selenazoles, using isosteric substitution. We synthesized 57 new chalcogen compounds which were evaluated against T. cruzi, C2C12 cells and cruzain, the main target of this parasite. Additionally, human cathepsin L, was tested for selectivity. Three compounds were selected, based on their activity against the intracellular amastigotes (EC50 < 1 μM, SI > 10) and cruzain (IC50 < 100 nM, SI > 5.55) which compared favorably with the approved drug, Benznidazole, and the well-established cruzain inhibitor K777. Seleno-compounds demonstrated enhanced activity and selenazoles showed a decrease in selenium-associated toxicity. Compound 4-methyl-2-(2-(1-(3-nitrophenyl)ethylidene)hydrazineyl)-1,3-selenazole (Se2h) emerged as a promising candidate, and its binding to cruzain was investigated. Pharmacokinetic assessment was conducted, showing a favorable profile for subsequent in vivo assays.

Azolium-Porphyrin Electrosynthesis.

Electrochemical oxidation of Zn(II) 2,7,12,17-tetra-tert-butylporphyrin in the presence of a series of azole derivatives (1-methylimidazole, 1-vinyl-1H-imidazole, 2-(1H-imidazol-1-yl)pyridine, 1-methylbenzimidazole, 1-methyl-1H-1,2,4-triazole, and benzothiazole) affords the corresponding meso-substituted azolium-porphyrins in very mild conditions and good yields. It was found that these nucleophiles were strongly ligated to the zinc(II) azolium-porphyrin complexes. Thus a demetalation/remetalation procedure was performed to recover the non-azole-coordinated zinc(II) complexes. X-ray crystallographic structures of three azolium-porphyrins were solved. Cyclic voltammetry analyses provided insight into the electron-withdrawing effect of the azolium substituents.

Photoinduced Copper-Catalyzed Cross-Coupling of Acylsilanes with Heteroarenes via Bimetallic Relay.

The transition metal-catalyzed direct coupling reactions involving electron-rich Fischer carbene species are largely underdeveloped and remain a big challenge. Here, a direct coupling reaction of azoles and azine N-oxides is reported with Fischer copper carbene species bearing an α-siloxy group i, which can be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. This coupling reaction between electron-rich α-siloxy Fischer Cu-carbene species with hard carbanion nucleophiles may undergo a bimetallic relay process, which is confirmed by the kinetic analysis and in situ NMR analysis. This reaction features mild conditions and remarkable heterocycle compatibility. Notably, this protocol tolerates a series of azole or azine N-oxide derivatives, including benzoxazole, benzothiazole, benzoimidazole, benzoisoxazole, oxazole, oxadiazole, triazolo[4,3-a]pyridine, purine, caffeine, pyridine N-oxide, quinoline N-oxide, pyrazine N-oxide, pyridazine N-oxide, etc. The synthetic value of this approach is demonstrated by the efficient synthesis of a histamine h4 receptor ligand and a marketed drug carbinoxamine.

2-Cyano-N-(2,5-dioxopyrrolidin-1-yl) acetamide as a building block for developing new azole and azine derivatives and assessing their biological properties

2-Cyano-N-(2,5-dioxopyrrolidin-1-yl) acetamide as a building block for developing new azole and azine derivatives and assessing their biological properties

The association of azole antifungals with overall survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors.

Preclinical data suggest antifungal azole derivatives have antitumor efficacy that may modulate response to immune checkpoint inhibitors (ICIs). We aimed to evaluate the association of azole drugs with overall survival (OS) in a population of patients with non-small cell lung cancer (NSCLC) treated with ICI within the Veterans Health Administration (VHA). In this retrospective study, the VA Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant oral azole use was defined as dispensation by a VA pharmacy within 90 days of the first ICI infusion. Patients who received azole after 30 days were excluded from the analysis to mitigate immortal time bias. OS was measured from the start of ICI. Cox regression and propensity score matching were used to adjust for confounders. We identified 3413 patients with NSCLC receiving ICI; 324 (9.5%) were exposed to concomitant azoles. As a group, azole use was not associated with OS (hazard ratio [HR] = 0.96; 95% CI, 0.84-1.09; P = .51). After stratification by azole type, clotrimazole had an association with better OS on univariable (HR = 0.75; 95% CI, 0.59-0.96; P = .024) and multivariable analysis (HR = 0.71; 95% CI, 0.56-0.91; P = .007). Propensity score matching of patients who received clotrimazole vs no azole yielded 101 patients per matched cohort. Clotrimazole was associated with improved OS, although this did not meet the threshold for statistical significance (HR = 0.74; 0.54-1.01; P = .058). This observational study demonstrated an association between clotrimazole and OS among patients with advanced NSCLC receiving ICI. These findings build upon preclinical evidence and support further investigation into the potential for clotrimazole as a repurposed FDA drug to improve cancer outcomes.

A Review on Analytical Methods of Anti-fungal Agents used for the Treatment of Onychomycosis

Background: Analytical methods have an essential function in the healthcare sector, particularly when it emanates from the creation and approval of medications. These methods are essential for identifying the active ingredients, ensuring the purity of compounds, and quantifying the existence of any impurities or degradation products. Objective: The objective of the research article is to discuss an analytical method available for the drug Onychomycosis, which is indeed crucial in treating nail infection, to confirm the efficacy and quality of pharmaceutical products. Among various analytical techniques available, UV Spectroscopy, RP-HPLC (high performance-liquid chromatography) and tandem mass spectrometry are normally employed due to their speed and accuracy. Method: Literature surveys typically reveal the predominance of UV, RP-HPLC and LC-MS/MS methods for estimating azole derivatives due to their established reliability, sensitivity, and applicability to an extensive range of compounds. Researchers often select the most suitable method based on factors such as sample complexity, sensitivity requirements, and available instrumentation. Results: This present art states most of the validation parameters like LOQ, Linearity range, Column and mobile phase used in different dosage forms as well as versatile techniques. Conclusion: This review article provides a comprehensive evaluation of various analytical methods employed in the estimation of antifungal agents, particularly those used to treat Onychomycosis. Onychomycosis, a prevalent infection on nails caused by fungi, demands precise and accurate analytical techniques to ensure the safety and effectiveness of antifungal therapies. In this review, we discussed and compared a range of analytical technologies, highlighting their applications and sensitivity in the context of Onychomycosis drug analysis. This critical assessment aims to guide researchers and practitioners in selecting the most suitable methods for their specific analytical needs.

Design, synthesis, and evaluation of antitumor activity in Pseudolaric acid B Azole derivatives: Novel and potent angiogenesis inhibitor via regulation of the PI3K/AKT and MAPK mediated HIF-1/VEGF signaling pathway

Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized and assessed for their capacity to suppress VEGF secretion in SiHa cells under hypoxic conditions. Notably, majority of these derivatives exhibited significant inhibition of VEGF protein secretion without inducing cytotoxicity. Among them, compound M2 displayed the most potent inhibitory activity, with an IC50 value of 0.68 μM, outperforming the lead compound PAB (IC50 = 5.44 μM). Compound M2 not only curbed the migration and angiogenesis of HUVECs under hypoxic conditions but also hindered the invasion of SiHa cells. Mechanistic investigations unveiled that compound M2 may impede the accumulation and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) in SiHa cells, thereby downregulating VEGF expression. This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis. Furthermore, compound M2 was observed to modulate the PI3K/AKT/mTOR and MAPK signaling pathways in tumor cells, thereby regulating HIF-1α translation and synthesis. In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.

Advancements in Combating Fungal Infections: A Comprehensive Review on the Development of Azole Hybrid Antifungals.

In this review, we have summarized antifungal agents containing potent azole analogues. The provided literature is related to the development and application of azole derivatives and has been accessed from electronic data bases such as Science direct, Google Scholar, and Pubmed using keywords such as "design, synthesis and evaluation", "azole hybrids", "diazole hybrids", "indazole derivatives", "imidazole derivatives", "triazole derivatives", "tetrazole derivatives" and related combinations. From this review, it was identified that azole derivatives with promising antifungal activity play a vital role in drug discovery and development. The literature revealed that azole derivatives can effectively fight several types of microorganisms, such as Candida albicans, Aspergillus niger, and others. The rational design and structure‒activity relationship of these compounds are discussed in this paper, highlighting their potential as effective therapeutic options against various fungal pathogens. Moreover, this work addresses the challenges and future directions in the development of azole hybrids. The results of docking studies of several of the hybrids that the researchers provided are also summarized. The current work attempts to review such innovations, which may lead to the preparation of novel therapeutics. More research is required to confirm their safety and effectiveness in clinical practices.

Reductive C−N Bond Formation of Nitroarenes Using Pd@rGO‐CuFe2O4 Magnetic Nanoparticles in Water towards the Synthesis of N‐Aryl Formamide and Azole Derivatives

Abstract.Reductive C−N bond generation strategies of nitroarenes to form N‐arylformamide and azole derivatives were developed under the influences of magnetically separable Pd@rGO‐CuFe2O4 nanoparticle‐catalyzed reaction conditions. These reactions proceed at a very low catalyst loading in H2O as the solvent, which leads to a higher percentage of yields (up to 96 %) of the products. The catalyst is recovered from the reaction medium by using an external magnet and recycled for four consecutive reaction cycles with a less amounts of leaching.

Synthesis, Characterization, DNA, Fluorescence, Molecular Docking, and Antimicrobial Evaluation of Novel Pd(II) Complex Containing O, S Donor Schiff Base Ligand and Azole Derivative

Pd(II) with the Schiff base ligand 2-Hydroxy-3-Methoxy Benzaldehyde-Thiosemicarbazone (HMBATSC) (L2) and 2-aminobenzothiazole (2-ABZ) (L1) was synthesized. The Schiff base ligand and the Palladium(II) complex were characterized by C.H.N.S, FT-IR, conductance studies, magnetic susceptibility, XRD, and TGA. From the elemental analysis and spectral data, the complex was proposed to have the formula [Pd(HMBATSC)(2-ABZ)H2O]. The interaction between the Pd(II) complex and DNA was examined through various methods, including UV–Vis spectroscopy, fluorescence techniques, and DNA viscosity titrations. The findings provided strong evidence that the interaction between the Pd(II) complex and DNA occurs through the intercalation mode. The analysis yielded the following values: a Stern–Volmer quenching constant (ksv) of 1.67 × 104 M−1, a quenching rate constant (kq) of 8.35 × 1011 M−1 s−1, a binding constant (kb) of 5.20 × 105 M−1, and a number of binding the sites (n) of 1.392. DFT studies suggest that the azole derivative may act as an electron donor through pyridine nitrogen, while the Schiff base ligand may act as an electron donor via oxygen and sulfur atoms. TDDFT calculations indicate that the intramolecular charge transfer from the Schiff base to Pd(II) is responsible for the complex’s fluorescence quenching. The powder X-ray diffraction data revealed that the complex is arranged in a monoclinic system. The resulting Pd(II) complex was investigated for its antimicrobial activity and demonstrated antibacterial efficiency. Interestingly, it showed potent activity against E. coli and E. niger that was found to be more powerful than that recorded for Neomycin.

Voriconazole and Beauvercin Loaded Niosomal Mucoadhesive Nanogel as an effective Treatment for the Management of Oral Candidiasis

Oral candidiasis is a fungal infection, which affects the oral mucosa. The main causative agent of this is Candida albicans and as the literature indicates highest prevalence of Candida bloodstream infections in India. Most commonly azole derivatives such as miconazole, fluconazole, itraconazol etc. are used to manage the infection. However, their efficacy is compromised due to multidrug resistance. A new azole derivative voriconzole could be effective but its poor water solubility and bioavailability are seen as significant limitations. Its efficacy can be enhanced by combining it with beauvericin, a cyclic hexadepsipeptide with remarkable antifungal activity against candida. One study reported that combining of beauvericin with voriconzole reduce the MIC of voriconazole by 128th times. Furthermore the solubility and bioavailability were enhanced by loading both the drugs in niosomes. The niosomes were imcorporated into a polymeric mucoadhesive gel post statistically optimization by the Box-Behnken experimental design. The niosomes were subjected to evaluation for vesicular size, surface morphology, entrapment efficiency, drug release and zeta potential High entrapment efficiency was observed in the optimized noisome formulation F3 (89.89±0.64 % for voriconazole and 92.98±0.35 % for beauvericin) exhibiting cumulative drug release of 79.98±1.87 % for voriconazole and 69.17±1.98 % for beauvericin. The mucoadhesive gel was smooth, homogenious with desired pH and mucodhesion. The stability studies indicated that all the formulations are stable as evidence by no significant change in drug content over the time. These findings suggest that a niosmal mucoadhesive gel loaded with voriconazole and beauvericin is a good therapeutic delivery system for the effective treatment of oral candidiasis.

Novel Ferrocenyl‐azole Derivatives: Synthesis, DFT Calculation and Unlocking the Anticancer Potential

AbstractHerein, a series of novel ferrocenyl/phenyl/thiophenyl‐azoles was disclosed by vinylic amination of ferrocenyl/phenyl/thiophenyl substituted β‐chloro cinnamaldehydes and acrylonitriles. A highly economical and robust chalcogen‐stabilized iron selenide carbonyl cluster Fe3Se2(CO)9 worked as an efficient catalyst under aerobic conditions. The amination of ferrocenyl/phenyl/thiophenyl substituted β‐chloro‐vinylic Csp2‐Cl with azole derivatives was fully established and fabrication of the Csp2‐N bond was completely supported by various spectral analysis. Moreover, wide range of substrates with functionally different azoles were investigated for the present reaction and good to excellent transformation was recorded. Some of the selected ferrocenated azole derivatives were screened for anti‐cancer activity against the prostate cancer cells (PC‐3) and found to be highly active at low concentration of 5.77 μM with IC50 value. Furthermore, HOMO and LUMO levels and energy gap of some selected compounds were calculated by the density functional theory (DFT).

Microemulsion as Novel Drug Delivery for Fungal Eye Infection

The cornea, orbit, and other ocular tissues may get infected by fungi. Ophthalmic mycoses, often known as ocular fungal infections, are a significant cause of morbidity and blindness. For fungus infections, a brand-new azole derivative has been authorized. New immunological techniques would also be beneficial in the future for enhancing patient outcomes. Treatment of ocular illnesses presents a significant barrier in terms of getting medications into the eyes using traditional drug delivery methods, such as solutions. The main barriers are those between blood and the eyes, between lachrymal fluid and the eyes, and between medication losses from the ocular surface brought on by lachrymal fluid secretion. To increase the bioavailability and lengthen the residence duration of medications administered topically to the eye, a variety of ocular drug delivery carriers have been developed. The microemulsion is created using the PHASE TITRATION METHOD. Due to the dual hydrophilic and lipophilic properties of microemulsions, the loaded medications can diffuse passively and become significantly partitioned in the varying lipophilic-hydrophilic ocular barrier. This abstract will provide details on the microemulsions used to treat fungal infections of the eyes.

Study on the Antifungal Activity of Gallic Acid and Its Azole Derivatives against Fusarium graminearum.

The wheat scab caused by Fusarium graminearum (F. graminearum) has seriously affected the yield and quality of wheat in China. In this study, gallic acid (GA), a natural polyphenol, was used to synthesize three azole-modified gallic acid derivatives (AGAs1-3). The antifungal activity of GA and its derivatives against F. graminearum was studied through mycelial growth rate experiments and field efficacy experiments. The results of the mycelial growth rate test showed that the EC50 of AGAs-2 was 0.49 mg/mL, and that of AGAs-3 was 0.42 mg/mL. The biological activity of AGAs-3 on F. graminearum is significantly better than that of GA. The results of field efficacy tests showed that AGAs-2 and AGAs-3 significantly reduced the incidence rate and disease index of wheat scab, and the control effect reached 68.86% and 72.11%, respectively. In addition, preliminary investigation was performed on the possible interaction between AGAs-3 and F. graminearum using density functional theory (DFT). These results indicate that compound AGAs-3, because of its characteristic of imidazolium salts, has potential for use as a green and environmentally friendly plant-derived antifungal agent for plant pathogenic fungi.

Azoles display promising anticonvulsant effects through possible PPAR-α activation

Azoles such as nafimidone, denzimol and loreclezole are known for their clinical efficacy against epilepsy, and loreclezole acts by potentiating γ-aminobutyric acid (GABA)-ergic currents. In the current study, we report a series of azole derivatives in alcohol ester and oxime ester structure showing promising anticonvulsant effects in 6 Hz and maximal electro shock (MES) models with minimal toxicity. The most promising of the series, 5f, was active in both 6 Hz and MES tests with a median effective dose (ED50) of 118.92 mg/kg in 6 Hz test and a median toxic dose (TD50) twice as high in mice. The compounds were predicted druglike and blood–brain barrier (BBB) penetrant in silico. Contrary to what was expected, the compounds showed no in vitro affinity to GABAA receptors (GABAARs) in radioligand binding assays; however, they were found structurally similar to peroxisome proliferator-activated receptors alpha (PPAR-α) agonists and predicted to show high affinity and agonist-like binding to PPAR-α in molecular docking studies. As a result, 5f emerged as a safe azole anticonvulsant with a wide therapeutic window and possible action through PPAR-α activation.

Epidemiological Profile of Microorganisms Associated with Female Infertility at the Mother and Child University Hospital Center of N’Djamena: Risk Factors and Antibiotic Resistance

Aims: the objective of this work was to determine the resistance phenotypes and the epidemiological profile of microorganisms associated with female infertility at the CHU-ME of N’Djamena.&#x0D; Materials and Methods: we conducted a prospective, cross-sectional and analytical study on women admitted for maternity desire at the CHU-ME of N'Djamena and consenting from June 1, 2022 to February 26, 2023. Isolation and identification microorganisms responsible for female infertility were carried out in the laboratories using standard clinical microbiology methods.&#x0D; Results: Of the 122 patients included in this series due to infertility, 88 (72.13%) tested positive for microbial infection compared to 34 (28%) negative tests (p = 0.01). The average age of infertile women was 34.24 years with extremes ranging from 19 to 45 years. The age groups most affected were 25 to 31 and 32 to 38. Primary infertility was 71.31% and secondary 28.68%. The microorganisms most associated with infertility were Chlamydia trachomatis (25.30%), Mycoplasma hominis (17.90%), Candida albicans (16.66%) and Staphylococcus aureus (16.04%) Streptococcus agalactiae (10 .49%) and Ureaplasma spp (8.14%). The risk factors most associated with infertility were advanced age (18.85%), surgical interventions (17.25%) and ovulation disorders (19.39%). The antecedents most associated with infertility were cesarean section 44 (36.07%) followed by miscarriages 29 (23.77).&#x0D; The sensitivity of bacterial and fungal agents to antibiotics and antifungals was varied. The majority of bacteria were resistant to Cyclins, Betalactams and Macrolides with proportions of 66%, 47.66% and 34% respectively. Strains of Ureaplasma spp and Mycoplasma homonis develop average resistances of 86.52% and 36.16% respectively against fluoroquinolones.&#x0D; The fungal strains were sensitive (54.33%) to the azole derivatives and resistant (70%) to the polyenes tested.&#x0D; Conclusion: The present study made it possible to determine high prevalence of microorganisms and risk factors associated with female infertility. It also highlighted high prevalence of resistance of bacteria to beta-lactams and fluoroquinolones and of Candida albicans to polyenes.

Peptides antimicrobiens : une nouvelle alternative pour le traitement des aspergilloses

Aspergillus fumigatus is the predominant fungal species causing pulmonary aspergillosis. The present-day anti-aspergillosis arsenal is limited, with a number of molecules occasioning severe side effects (amphotericin B) or provoking significant drug interactions (azole derivatives). Moreover, the recent emergence of azole-resistant A.fumigatus strains is a cause for concern. In this context, antimicrobial peptides (AMPs) are emerging as a promising therapeutic approach and alternative or complement to conventional antifungals.

Study of the effect of bifonazole concentration on the antifungal activity of vaginal suppositories

The analysis of the current state of pharmacotherapy for vulvovaginal candidiasis reveals that there is a contemporary need for the development of soft dosage forms for the local treatment of infectious diseases affecting the vulva and vagina. This should be based on azole derivatives that, despite possessing a well-established wide spectrum of antifungal and antibacterial effects, have not been utilized for vaginal administration in domestic formulations. The successful realization of this project would enable the field of domestic dermatology to provide effective, compliant, and affordable drugs for gynecological practice to the general population of Ukraine. Additionally, it would establish a viable alternative to imported pharmacotherapeutic agents. Aim. The purpose of this work is the scientific substantiation of the concentration of bifonazole in suppository compositions for vaginal use. Materials and methods. Research was conducted to investigate the influence of bifonazole concentration ranging from 1 % to 15 % in soft dosage forms for vaginal use. Model compositions were formulated on a polyethylene oxide carrier, considering its solubility. The antifungal activity of the experimental suppository compositions was chosen as the optimization parameter and assessed using the diffusion method in agar against Candida albicans ATCC 885-653. Variance analysis of the results revealed a significant impact of bifonazole concentration on the antimycotic activity of the suppository compositions based on the model polyethylene oxide. Results. The research results show that increasing the concentration of the active pharmaceutical ingredient in suppository masses above 10 % does not lead to a statistically significant increase in their antimycotic activity. Conclusions. As a result of the conducted study on the antifungal effect of suppository masses with bifonazole on a model polyethylene oxide basis, it was found that the concentration of the active pharmaceutical ingredient has a statistically significant effect on the effectiveness of the soft dosage form. It was established that a ten percent concentration of bifonazole, equivalent to 0.3 g of the biologically active substance in vaginal suppositories, provides the optimal level of their antifungal effect.

Human adenovirus type 3 restores pharmacologically inhibited exosomal cargo in lung carcinoma cells.

Introduction: Drug repurposing is fast growing and becoming an attractive approach for identifying novel targets, such as exosomes for cancer and antiviral therapy. Exosomes are a specialized class of extracellular vesicles that serve as functional mediators in intercellular communication and signaling that are important in normal physiological functions. A continuously growing body of evidence has established a correlation between the abnormal release of exosomes with various viral disease pathologies including cancer. Cells that are virus-infected release exosomes known to influence the process via the loading and transfer of viral components, such as miRNA, small (s) RNA, DNA, and proteins. Inhibition of exosome release may abate the spread and severity of viral infection, thus making exosomes an attractive target for antiviral therapies. We previously demonstrated the pharmacological inhibition of exosomes. Methods: Herein, we used a cell-based assay to determine the effect of Human adenovirus type 3 (HAdV3) on the exosome inhibition process by azole and Heparin derivatives. HAdV3-infected cells were treated with two concentrations of each inhibitor at different time points. Results: HAdV3 activities led to increased total sRNA, DNA, and exosome particle concentrations via particle tracking in the presence of Climbazole and Heparin relative to uninfected exosomes. In addition, there was an increased expression of classical markers such as ALG-2 interacting protein X (ALIX), and tetraspanin (CD63), (p < 0.05) and upregulated transcription factor interferon regulatory factor (IRF) 8 in the presence of HAdV3 after 24hours (h) of treatment. Whereas higher concentrations of Climbazole and Heparin sodium salt were found to inhibit total exosome protein (p < 0.001) and exo-RNA (p < 0.01) content even in the presence of HAdV3 relative to infected exosomes only. Activities of HAdV3 in the presence of selected inhibitors resulted in the positive regulation of exosome related DNA damage/repair signaling proteins. Blocking exosome secretion partially obstructed viral entry. Immunological studies revealed that HAdV3 fiber protein levels in A549 cells were reduced at all concentrations of Climbazole and Heparin and both multiplicities of infections (p < 0.001). Discussion: Our findings suggest that while HAdV may bolster inhibited exosome content and release when modulating certain activities of the endosomal pathway mediators, HAdV entry might be constrained by the activities of these pharmacological agents.