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Potato tubers are reproductive and storage organs, enabling their survival. Unraveling the molecular mechanisms that regulate tuberization is crucial for understanding how potatorespond to environmental stress situations and for potato breeding. Previously, we did a transcriptomic analysis of potato microtuberization without light. This showed that important cellular processes like ribosomal proteins, cell cycle, carbon metabolism, oxidative stress, fatty acids, and phytosterols (PS) biosynthesis were closely connected in a protein-protein interaction (PPI) network. Research on PS function during potato tuberization has been scarce. PS plays a critical role in regulating membrane permeability and fluidity, and they are biosynthetic precursors of brassinosteroids (BRs) in plants, which are critical in regulating gene expression, cell division, differentiation, and reproductive biology. Within a PPI network, we found a module of 15 genes involved in the PS biosynthetic process. Darkness, as expected, activated the mevalonate (MVA) pathway. There was a tight interaction between three coding gene products for HMGR3, MVD2, and FPS1, and the gene products that synthetize PS, including CAS1, SMO1, BETAHSD, CPI1, CYP51, FACKEL, HYDRA1, SMT2, SMO2, STE1, and SSR1. Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed the expression analysis of ten specific genes involved in the biosynthesis of PS. This manuscript discusses the potential role of genes involved in PS biosynthesis during microtuber development.

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Natural product offers an ocean of biologically active compounds that have diverse functionality. Thus, the present study aims for the exploration of natural product molecules for their leishmanicidal potency. Primary evaluation at 50 µM concentration revealed that out of 560 molecules, 38 compounds demonstrated a percentage killing of >50%. Next, the dose-dependent investigation showed that six active hits displayed the IC50 value ranging from 0.47 to 14.2 µM. Further, the molecular docking analysis using the alpha fold structure of Sterol C-24 methyltransferase of Leishmania donovani (LdSMT) (an enzyme absent in mammalian host) unveiled the strong binding affinity with top two hits namely shatavarin IV (-7.9 kcal/mol) and 6-methoxydihydrochelerythrine (-7.6 kcal/mol). Also, in silico studies were supported by the alterations in ergosterol content in the parasites treated with these two potent hits. In conclusion, our study suggests that the two potent hits inhibit the Leishmania parasite growth by hindering sterol biosynthesis.

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Secondary metabolites play multiple crucial roles in plants by modulating various regulatory networks. The biosynthesis of these compounds is unique to each species and is intricately controlled by a range of developmental and environmental factors. While light's role in certain secondary metabolites is evident, its impact on sterol biosynthesis remains unclear. Previous studies indicate that ELONGATED HYPOCOTYL5 (HY5), a bZIP transcription factor, is pivotal in skotomorphogenesis to photomorphogenesis transition. Additionally, PHYTOCHROME INTERACTING FACTORs (PIFs), bHLH transcription factors, act as negative regulators. To unveil the light-dependent regulation of the mevalonic acid (MVA) pathway, a precursor for sterol biosynthesis, mutants of light signaling components, specifically hy5-215 and the pifq quadruple mutant (pif 1,3,4, and 5), were analyzed in Arabidopsis thaliana. Gene expression analysis in wild-type and mutants implicates HY5 and PIFs in regulating sterol biosynthesis genes. DNA-protein interaction analysis confirms their interaction with key genes like AtHMGR2 in the rate-limiting pathway. Results strongly suggest HY5 and PIFs' pivotal role in light-dependent MVA pathway regulation, including the sterol biosynthetic branch, in Arabidopsis, highlighting a diverse array of light signaling components finely tuning crucial growth pathways.

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7-Dehydrocholesterol (7-DHC) is widely present in various organisms and is an important precursor of vitamin D3. Despite significant improvements in the biosynthesis of 7-DHC, it remains insufficient to meet the industrial demands. In this study, we reported high-level production of 7-DHC in an industrial Saccharomyces cerevisiae leveraging subcellular organelles. Initially, the copy numbers of DHCR24 were increased in combination with sterol transcriptional factor engineering and rebalanced the redox power of the strain. Subsequently, the effects of compartmentalizing the post-squalene pathway in peroxisomes were validated by assembling various pathway modules in this organelle. Furthermore, several peroxisomes engineering was conducted to enhance the production of 7-DHC. Utilizing the peroxisome as a vessel for partial post-squalene pathways, the potential of yeast for 7-dehydrocholesterol production was demonstrated by achieving a 26-fold increase over the initial production level. 7-DHC titer reached 640.77 mg/L in shake flasks and 4.28 g/L in a 10 L bench-top fermentor, the highest titer ever reported. The present work lays solid foundation for large-scale and cost-effective production of 7-DHC for practical applications.

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Parthenium hysterophorus plant has a diverse chemical profile and immense bioactive potential. It exhibits excellent pharmacological properties such as anti-cancer, anti-inflammatory, anti-malarial, microbicidal, and anti-trypanosomal. The present study aims to evaluate the anti-leishmanial potential and toxicological safety of anhydroparthenin isolated from P. hysterophorus. Anydroparthenin was extracted from the leaves of P. hysterophorus and characterized through detailed analysis of 1H, 13C NMR, and HRMS. Dye-based in vitro and ex vivo assays confirmed that anhydroparthenin significantly inhibited both promastigote and amastigote forms of the Leishmania donovani parasites. Both the cytotoxicity experiment and hemolytic assay revealed its non-toxic nature and safety index in the range of 10 to 15. Further, various mechanistic assays suggested that anhydroparthenin led to the generation of oxidative stress, intracellular ATP depletion, alterations in morphology and mitochondrial membrane potential, formation of intracellular lipid bodies, and acidic vesicles, ultimately leading to parasite death. As a dual targeting approach, computational studies and sterol quantification assays confirmed that anhydroparthenin inhibits the Sterol C-24 methyl transferase and Sterol 14-α demethylase proteins involved in the ergosterol biosynthesis in Leishmania parasites. These results suggest that anhydroparthenin could be a promising anti-leishmanial molecule and can be developed as a novel therapeutic stratagem against leishmaniasis.

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Plant-microbe interactions (PMIs) are regulated through a wide range of mechanisms in which sterols from plants and microbes are involved in numerous ways, including recognition, transduction, communication, and/or exchanges between partners. Phytosterol equilibrium is regulated by PMIs through expression of genes involved in phytosterol biosynthesis, together with their accumulation. As such, PMI outcomes also include plasma membrane (PM) functionalization events, in which phytosterols have a central role, and activation of sterol-interacting proteins involved in cell signaling. In spite (or perhaps because) of such multifaceted abilities, an overall mechanism of sterol contribution is difficult to determine. However, promising approaches exploring sterol diversity, their contribution to PMI outcomes, and their localization would help us to decipher their crucial role in PMIs.

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Phytosterols are vital structural and regulatory components in plants. Zea mays produces a series of phytosterols that are specific to corn. However, the underline biosynthetic mechanism remains elusive. In this study, we identified a novel sterol methyltransferase from Z. mays (ZmSMT1-2) which showed a unique feature compared with documented plant SMTs. ZmSMT1-2 showed a substrate preference for cycloartenol. Using S-adenosyl-L-methionine (AdoMet) as a donor, ZmSMT1-2 converted cycloartenol into alkylated sterols with unique side-chain architectures, including Δ25(27) (i.e., cyclolaudenol and cycloneolitsol) and Δ24(25) (i.e., cyclobranol) sterols. Cycloneolitsol is identified as a product of SMTs for the first time. Our discovery provides a previously untapped mechanism for phytosterol biosynthesis and adds another layer of diversity of sterol biosynthesis.

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The 14α-demethylation step is critical in eukaryotic sterol biosynthesis, catalyzed by cytochrome P450 (P450) Family 51 enzymes, for example, with lanosterol in mammals. This conserved three-step reaction terminates in a C-C cleavage step that generates formic acid, the nature of which has been controversial. Proposed mechanisms involve roles of P450 Compound 0 (ferric peroxide anion, FeO2 - ) or Compound I (perferryl oxygen, FeO3+ ) reacting with either the aldehyde or its hydrate, respectively. Analysis of 18 O incorporation into formic acid from 18 O2 provides a means of distinguishing the two mechanisms. Human P450 51A1 incorporated 88 % 18 O (one atom) into formic acid, consistent with a major but not exclusive FeO2 - mechanism. Two P450 51 orthologs from amoeba and yeast showed similar results, while two orthologs from pathogenic trypanosomes showed roughly equal contributions of both mechanisms. An X-ray crystal structure of the human enzyme showed the aldehyde oxygen atom 3.5 Šaway from the heme iron atom. Experiments with human P450 51A1 and H2 18 O yielded primarily one 18 O atom but 14 % of the formic acid product with two 18 O atoms, indicative of a minor contribution of a Compound I mechanism. LC-MS evidence for a Compound 0-derived Baeyer-Villiger reaction product (a 14α-formyl ester) was also found.

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The biosynthesis of C27-29 sterols from their C30 precursor squalene involves C24-alkylation and the removal of three methyl groups, including two at the C4 position. The two C4 demethylation reactions require a bifunctional enzyme known as 3ß-hydroxysteroid dehydrogenase/C4-decarboxylase (3ßHSD/D), which removes an oxidized methyl (carboxylic) group at C4 while simultaneously catalyzing the 3ß-hydroxyl→3-keto oxidation. Its loss-of-function mutations cause ergosterol-dependent growth in yeast and congenital hemidysplasia with ichthyosiform erythroderma and limb defect (CHILD) syndrome in humans. Although plant 3ßHSD/D enzymes were well studied enzymatically, their developmental functions remain unknown. Here we employed a CRISPR/Cas9-based genome-editing approach to generate knockout mutants for two Arabidopsis 3ßHSD/D genes, HSD1 and HSD2, and discovered the male gametophytic lethality for the hsd1 hsd2 double mutation. Pollen-specific expression of HSD2 in the heterozygous hsd1 hsd2/+ mutant not only rescued the pollen lethality but also revealed the critical roles of the two HSD genes in embryogenesis. Our study thus demonstrated the essential functions of the two Arabidopsis 3ßHSD/D genes in male gametogenesis and embryogenesis.

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Sterols constitute vital structural and regulatory components of eukaryotic cells. In the oleaginous microorganism Schizochytrium sp. S31, the sterol biosynthetic pathway primarily produces cholesterol, stigmasterol, lanosterol, and cycloartenol. However, the sterol biosynthesis pathway and its functional roles in Schizochytrium remain unidentified. Through Schizochytrium genomic data mining and a chemical biology approach, we first in silico elucidated the mevalonate and sterol biosynthesis pathways of Schizochytrium. The results showed that owing to the lack of plastids in Schizochytrium, it is likely to use the mevalonate pathway as the terpenoid backbone pathway to supply isopentenyl diphosphate for the synthesis of sterols, similar to that in fungi and animals. In addition, our analysis revealed a chimeric organization of the Schizochytrium sterol biosynthesis pathway, which possesses features of both algae and animal pathways. Temporal tracking of sterol profiles reveals that sterols play important roles in Schizochytrium growth, carotenoid synthesis, and fatty acid synthesis. Furthermore, the dynamics of fatty acid and transcription levels of genes involved in fatty acid upon chemical inhibitor-induced sterol inhibition reveal possible co-regulation of sterol synthesis and fatty acid synthesis, as the inhibition of sterol synthesis could promote the accumulation of fatty acid in Schizochytrium. Sterol and carotenoid metabolisms are also found possibly co-regulated, as the inhibition of sterols led to decreased carotenoid synthesis through down-regulating the gene HMGR and crtIBY in Schizochytrium. Together, elucidation of the Schizochytrium sterol biosynthesis pathway and its co-regulation with fatty acid synthesis lay the essential foundation for engineering Schizochytrium for the sustainable production of lipids and high-value chemicals.

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Sterols are essential components of eukaryotic cell membranes. However, studies on sterol biosynthesis in bryophytes are limited. This study analyzed the sterol profiles in the bryophyte model plant Marchantia polymorpha L. The thalli contained typical phytosterols such as campesterol, sitosterol and stigmasterol. BLASTX analysis of the M. polymorpha genome against the Arabidopsis thaliana sterol biosynthetic genes confirmed the presence of all the enzymes responsible for sterol biosynthesis in M. polymorpha. We further focused on characterizing two genes, MpDWF5A and MpDWF5B, which showed high homology with A. thaliana DWF5, encoding Δ5,7-sterol Δ7-reductase (C7R). Functional analysis using a yeast expression system revealed that MpDWF5A converted 7-dehydrocholesterol to cholesterol, indicating that MpDWF5A is a C7R. Mpdwf5a-knockout (Mpdwf5a-ko) lines were constructed using CRISPR/Cas9-mediated genome editing. Gas chromatography-mass spectrometry analysis of Mpdwf5a-ko revealed that phytosterols such as campesterol, sitosterol and stigmasterol disappeared, and instead, the corresponding Δ7-type sterols accumulated. The thalli of Mpdwf5a-ko grew smaller than those of the wild type, and excessive formation of apical meristem in the thalli was observed. In addition, the gemma cups of the Mpdwf5a-ko were incomplete, and only a limited number of gemma formations were observed. Treatment with 1 µM of castasterone or 6-deoxocastasterone, a bioactive brassinosteroid (BR), partly restored some of these abnormal phenotypes, but far from complete recovery. These results indicate that MpDWF5A is essential for the normal growth and development of M. polymorpha and suggest that the dwarfism caused by the Mpdwf5a-ko defect is due to the deficiency of typical phytosterols and, in part, a BR-like compound derived from phytosterols.

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Oteseconazole was approved by the US FDA in April 2022. It is the first approved selective and orally bioavailable CYP51 inhibitor for the treatment of patients with recurrent Vulvovaginal candidiasis. Herein, we describe its dosage, administration, chemical structure, physical properties, synthesis, mechanism of action, and pharmacokinetics.

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Overproduction of reactive oxygen species (ROS) drives inflammation and mutagenesis. However, the role of the DNA damage response in immune responses remains largely unknown. Here we found that stabilization of the mismatch repair (MMR) protein MSH6 in response to alkylation damage requires interactions with the molybdopterin synthase associating complex (MPTAC) and Ada2a-containing histone acetyltransferase complex (ATAC). Furthermore, MSH6 promotes sterol biosynthesis via the mevalonate pathway in a MPTAC- and ATAC-dependent manner. MPTAC reduces the source of alkylating agents (ROS). Therefore, the association between MMR proteins, MPTAC, and ATAC promotes anti-inflammation response and reduces alkylating agents. The inflammatory responses measured by xanthine oxidase activity are elevated in Lymphoblastoid Cell Lines (LCLs) from some Fragile X-associated disorders (FXD) patients, suggesting that alkylating agents are increased in these FXD patients. However, MPTAC is disrupted in LCLs from some FXD patients. In LCLs from other FXD patients, interaction between MSH6 and ATAC was lost, destabilizing MSH6. Thus, impairment of MPTAC and ATAC may cause alkylation damage resistance in some FXD patients.

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The emergence of antifungal resistance, especially to the most widely used azole class of ergosterol biosynthesis inhibitors, makes fungal infections difficult to treat in clinics and agriculture. When exposed to azoles, fungi can make adaptive responses to alleviate azole toxicity and produce azole tolerance. However, except for azole efflux pumps and ergosterol biosynthesis genes, the role of most azole responsive genes in azole resistance is unknown. In this study, STK-17, whose transcription is upregulated by azoles, was characterized as a novel kinase that is required for azole resistance. Deletion or dysfunction of STK-17 led to azole hypersensitivity in Neurospora crassa and to other ergosterol biosynthesis inhibitors such as amorolfine, terbinafine, and amphotericin B, but not fatty acid and ceramide biosynthesis inhibitors. STK-17 was also required for oxidative stress resistance, but this was not connected to azole resistance. RNA-seq results showed that stk-17 deletion affected the basal expression and the response to ketoconazole of some membrane protein genes, indicating functional association of STK-17 with the membrane. Notably, deletion of stk-17 affected the normal response to azoles of erg genes, including the azole target-encoding gene erg11, and erg2, erg6, and erg24, and led to abnormal accumulation of sterols in the presence of azoles. HPLC-MS/MS analysis revealed increased intracellular azole accumulation in the stk-17 mutant, possibly due to enhanced azole influx and reduced azole efflux that was independent of the major efflux pump CDR4. Importantly, STK-17 was widely distributed and functionally conserved among fungi, thus providing a potential antifungal target. IMPORTANCE Antifungal resistance is increasing worldwide, especially to the most widely used azole class of ergosterol biosynthesis inhibitors, making control of fungal infections more challenging. A lot of effort has been expended in elucidating the mechanism of azole resistance and revealing potential antifungal targets. In this study, by analyzing azole-responsive genes in Neurospora crassa, we discovered STK-17, a novel kinase, that is required for azole resistance in several types of fungi. It has a role in regulating membrane homeostasis, responses to azole by ergosterol biosynthesis genes and azole accumulation, thus, deepening our understanding on the mechanism of azole stress response. Additionally, STK-17 is conserved among fungi and plays important roles in fungal development and stress resistance. Kinase inhibitors are broadly used for treating diseases, and our study pinpoints a potential drug target for antifungal development.

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BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.

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The mortality rate of leishmaniasis is increasing at an alarming rate and is currently second to malaria amongst the other neglected tropical diseases. Unfortunately, many governments and key stakeholders are not investing enough in the development of new therapeutic interventions. The available treatment options targeting different pathways of the parasite have seen inefficiencies, drug resistance, and toxic side effects coupled with longer treatment durations. Numerous studies to understand the biochemistry of leishmaniasis and its pathogenesis have identified druggable targets including ornithine decarboxylase, trypanothione reductase, and pteridine reductase, which are relevant for the survival and growth of the parasites. Another plausible target is the sterol biosynthetic pathway; however, this has not been fully investigated. Sterol biosynthesis is essential for the survival of the Leishmania species because its inhibition could lead to the death of the parasites. This review seeks to evaluate how critical the enzymes involved in sterol biosynthetic pathway are to the survival of the leishmania parasite. The review also highlights both synthetic and natural product compounds with their IC50 values against selected enzymes. Finally, recent advancements in drug design strategies targeting the sterol biosynthesis pathway of Leishmania are discussed.

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Sterol biosynthesis, primarily associated with eukaryotic kingdoms of life, occurs as an abbreviated pathway in the bacterium Methylococcus capsulatus. Sterol 14α-demethylation is an essential step in this pathway and is catalyzed by cytochrome P450 51 (CYP51). In M. capsulatus, the enzyme consists of the P450 domain naturally fused to a ferredoxin domain at the C-terminus (CYP51fx). The structure of M. capsulatus CYP51fx was solved to 2.7 Å resolution and is the first structure of a bacterial sterol biosynthetic enzyme. The structure contained one P450 molecule per asymmetric unit with no electron density seen for ferredoxin. We connect this with the requirement of P450 substrate binding in order to activate productive ferredoxin binding. Further, the structure of the P450 domain with bound detergent (which replaced the substrate upon crystallization) was solved to 2.4 Å resolution. Comparison of these two structures to the CYP51s from human, fungi, and protozoa reveals strict conservation of the overall protein architecture. However, the structure of an "orphan" P450 from nonsterol-producing Mycobacterium tuberculosis that also has CYP51 activity reveals marked differences, suggesting that loss of function in vivo might have led to alterations in the structural constraints. Our results are consistent with the idea that eukaryotic and bacterial CYP51s evolved from a common cenancestor and that early eukaryotes may have recruited CYP51 from a bacterial source. The idea is supported by bioinformatic analysis, revealing the presence of CYP51 genes in >1,000 bacteria from nine different phyla, >50 of them being natural CYP51fx fusion proteins.

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The mechanisms underlying resistance of the Chagas disease parasite, Trypanosoma cruzi, to current therapies are not well understood, including the role of metabolic heterogeneity. We found that limiting exogenous glutamine protects actively dividing amastigotes from ergosterol biosynthesis inhibitors (azoles), independent of parasite growth rate. The antiparasitic properties of azoles are derived from inhibition of lanosterol 14α-demethylase (CYP51) in the endogenous sterol synthesis pathway. We find that carbons from 13C-glutamine feed into amastigote sterols and into metabolic intermediates that accumulate upon CYP51 inhibition. Incorporation of 13C-glutamine into endogenously synthesized sterols is increased with BPTES treatment, an inhibitor of host glutamine metabolism that sensitizes amastigotes to azoles. Similarly, amastigotes are re-sensitized to azoles following addition of metabolites upstream of CYP51, raising the possibility that flux through the sterol synthesis pathway is a determinant of sensitivity to azoles and highlighting the potential role for metabolic heterogeneity in recalcitrant T. cruzi infection.

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Despite the resistance problems in Monilinia fructicola, demethylation inhibitor fungicides (DMIs) are still effective for the disease management of brown rot in commercial stone fruit orchards in Brazil. This study aims to investigate the sensitivity of M. fructicola isolates and efficiency of DMIs to reduce brown rot. A set of 93 isolates collected from Brazilian commercial orchards were tested for their sensitivities to tebuconazole, propiconazole, prothioconazole, and myclobutanil. The isolates were analyzed separately according to the presence or absence of the G461S mutation in MfCYP51 gene, determined by allele-specific test. The mean EC50 values for G461S mutants and wild-type isolates were respectively 8.443 and 1.13 µg/ml for myclobutanil, 0.236 and 0.026 µg/ml for propiconazole, 0.115 and 0.002 µg/ml for prothioconazole, and 1.482 and 0.096 µg/ml for tebuconazole. The density distribution curves of DMI sensitivity for both genotypes showed that myclobutanil and prothioconazole curves were mostly shifted toward resistance and sensitivity, respectively. Incomplete cross-resistance was detected among propiconazole and tebuconazole in both wild-type (r = 0.45) and G461S (r = 0.38) populations. No cross-sensitivity was observed among wild-type isolates to prothioconazole and the others DMIs tested. Fungicide treatments on detached fruit inoculated with M. fructicola genotypes showed significant DMI efficacy differences when fruit were inoculated with wild-type and G461S isolates. Protective applications with prothioconazole were more effective for control of both G461S and wild-type isolates compared with tebuconazole. Curative applications with tebuconazole were most effective in reducing the incidence and lesion size of G461S isolates. Sporulation occurred only for G461S isolates treated with tebuconazole under curative and preventative treatments. The differences found among the performance of triazoles against M. fructicola isolates will form the basis for recommendations of rational DMI usage to control brown rot in Brazil.

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1,2,4-Triazole is a very important scaffold in medicinal chemistry due to the wide spectrum of biological activities and mainly antifungal activity of 1,2,4-triazole derivatives. The main mechanism of antifungal action of the latter is inhibition of 14-alpha-demethylase enzyme (CYP51). The current study presents synthesis and evaluation of eight triazole derivatives for their antimicrobial activity. Docking studies to elucidate the mechanism of action were also performed. The designed compounds were synthesized using classical methods of organic synthesis. The in vivo evaluation of antimicrobial activity was performed by microdilution method. All tested compounds showed good antibacterial activity with MIC and MBC values ranging from 0.0002 to 0.0069 mM. Compound 2 h appeared to be the most active among all tested with MIC at 0.0002-0.0033 mM and MBC at 0.0004-0.0033 mM followed by compounds 2f and 2g. The most sensitive bacterium appeared to be Xanthomonas campestris while Erwinia amylovora was the most resistant. The evaluation of antifungal activity revealed that all compounds showed good antifungal activity with MIC values ranging from 0.02 mM to 0.52 mM and MFC from 0.03 mM to 0.52 mM better than reference drugs ketoconazole (MIC and MFC values at 0.28-1.88 mM and 0.38 mM to 2.82 mM respectively) and bifonazole (MIC and MFC values at 0.32-0.64 mM and 0.64-0.81 mM). The best antifungal activity is displayed by compound 2 h with MIC at 0.02-0.04 mM and MFC at 0.03-0.06 mM while compound 2a showed the lowest activity. The results showed that these compounds could be lead compounds in search for new potent antimicrobial agents. Docking studies confirmed experimental results.

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