A COMPARATIVE CLINICAL STUDY ON TUVARAK TAILA CREAM AND 2 PERCENT TOPICAL KETOCONAZOLE IN THE MANAGEMENT OF SIDHMA KUSHTHA (PITYRIASIS VERSICOLOR) IN CHILDREN- AN OPEN LABELLED RANDOMIZED CONTROLLED CLINICAL TRIAL - NIL

开始日期2025-05-01

申办/合作机构-

NCT05638763 / Recruiting临床2期IIT

Cytochrome P450 Inhibition With Ketoconazole to Decrease Dosage and Costs of Dasatinib for Chronic Myelogenous Leukemia

This phase 2 single-arm study aims to demonstrate the efficacy of strong cytochrome inhibition with ketoconazole to reduce dasatinib dosage for adults with chronic myelogenous leukemia. Researchers will describe response rates and adverse events.

开始日期2024-11-01

申办/合作机构

Hospital Universitario. Dr. José Eleuterio González

CTRI/2024/10/074571 / Not yet recruiting临床2期IIT

Randomized controlled clinical trial to evaluate the efficacy of Somraji Taila in DadruKushtha (Dermatophytosis) in children - NIL

开始日期2024-10-10

申办/合作机构-

100 项与 C14DM 相关的临床结果

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100 项与 C14DM 相关的转化医学

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0 项与 C14DM 相关的专利（医药）

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230

项与 C14DM 相关的文献（医药）

2024-12-01·Microbiological Research

A ubiquitin-mediated post-translational degradation of Cyp51A contributes to a novel azole resistance mode in Aspergillus fumigatus

Article

作者: Zhang, Yuanwei ; Zhu, Guoxing ; Lu, Ling ; Fu, Mengjuan

The airborne fungus Aspergillus fumigatus is a major pathogen that poses a serious health threat to humans by causing aspergillosis. Azole antifungals inhibit sterol 14-demethylase (encoded by cyp51A), an enzyme crucial for fungal cell survival. However, the most common mechanism of azole resistance in A. fumigatus is associated with the mutations in cyp51A and tandem repeats in its promoter, leading to reduced drug-enzyme interaction and overexpression of cyp51A. It remains unknown whether post-translational modifications of Cyp51A contribute to azole resistance. In this study, we report that the Cyp51A expression is highly induced upon exposure to itraconazole, while its ubiquitination level is significantly reduced by itraconazole. Loss of the ubiquitin-conjugating enzyme Ubc7 confers resistance to multiple azole antifungals but hinders hyphal growth, conidiation, and virulence. Western blot and immunoprecipitation assays show that deletion of ubc7 reduces Cyp51A degradation by impairing its ubiquitination, thereby leading to drug resistance. Most importantly, the overexpression of ubc7 in common environmental and clinical azole-resistant cyp51A isolates partially restores azole sensitivity. Our findings demonstrate a non-cyp51A mutation-based resistance mechanism and uncover a novel role of post-translational modification in contributing to azole resistance in A. fumigatus.

2024-11-01·Infectious Disorders - Drug Targets

An Insight into the Repurposing of Phytoconstituents obtained from Delhi’s Aravalli Biodiversity Park as Antifungal Agents

Article

作者: Sharma, Neetika ; Sharma, Kalicharan ; Aggarwal, Geeta ; Kaur, Amanpreet

Abstract:The global prevalence of fungal infections is alarming in both the pre- and postCOVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment strategies for fungal infections due to toxic potential, drug interactions, and the development of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules showing promise against these targets are reviewed. The objective was to predict or repurpose phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-αdemethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India, to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands were collected, and virtual screening was performed using Schrodinger Suite 2016 software to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After analysis of docking results, ligands were selected based on their interaction against both the target proteins and comparison with respective standard ligands (fluconazole and ganetespib). We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively) and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking protocol was validated and MM/GBSA studies depicted better stability of selected three ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex. Further, MD simulation studies were performed using the Desmond (67) software package version 2018-4. All the findings are presented as a case study for the prediction of dual targets for the repurposing of certain phytochemicals as antifungal agents.

2024-10-18·Archives of microbiology

Investigating role of positively selected genes and mutation sites of ERG11 in drug resistance of Candida albicans.

Article

作者: Palia, Dushyant ; Kumar, Chandan ; Fandilolu, Prayagraj ; Idicula-Thomas, Susan

The steep increase in acquired drug resistance in Candida isolates has posed a great challenge in the clinical management of candidiasis globally. Information of genes and codon sites that are positively selected during evolution can provide insights into the mechanisms driving antifungal resistance in Candida. This study aimed to create a manually curated list of genes of Candida spp. reported to be associated with antifungal resistance in literature, and further investigate the structure-function implications of positively selected genes and mutation sites. Sequence analysis of antifungal drug resistance associated gene sequences from various species and strains of Candida revealed that ERG11 and MRR1 of C. albicans were positively selected during evolution. Four sites in ERG11 and two sites in MRR1 of C. albicans were positively selected and associated with drug resistance. These four sites (132, 405, 450, and 464) of ERG11 are predictive markers for azole resistance and have evolved over time. A well-characterized crystal structure of sterol-14-α-demethylase (CYP51) encoded by ERG11 is available in PDB. Therefore, the stability of CYP51 in complex with fluconazole was evaluated using MD simulations and molecular docking studies for two mutations (Y132F and Y132H) reported to be associated with azole resistance in literature. These mutations induced high flexibility in functional motifs of CYP51. It was also observed that residues such as I304, G308, and I379 of CYP51 play a critical role in fluconazole binding affinity. The insights gained from this study can further guide drug design strategies addressing antimicrobial resistance.