List of plant components having antifungal property [ 29 ]. Novel drug delivery system has shown tremendous potential to deliver herbal drugs in the form of microcapsules, implants, nanoparticles micro particles sustained release tablets or extended release forms.

Many herbal drugs using novel drug delivery system has made a mark in the market and few of them are in the developmental stage in the laboratory [ 30 ].

Active herbal components such as curcumin, digoxin, atropine, bromelain can be promising prospects for treatment of conditions like cancer or inflammation [ 31 ]. The popularity experienced by novel drug delivery system is due to its ability to deliver the herbal drugs in a better way providing enhanced therapeutic efficacy with lower toxicity [ 32 ].

In addition to this it also counteract the limitations of lower absorption and lack of specificity experienced by the available formulation of drugs. Advantages of novel drug delivery system over the presently available drug therapy is that it is specific, has rapid onset of action with faster absorption due to enhanced surface area and lastly nanoparticles provides better penetration in Blood Brain Barrier BBB [ 33 ].

For any herbal drugs to show expected therapeutic efficacy optimum amount of active constituent must reach the target tissues. Herbal drugs are prone to be degraded by first pass metabolism of by the pH difference of GIT.

Various novel drug delivery systems such as nanoparticles, nanoemulsions, phytosomes, transferosomes and liposomes by passes all the hurdles of acidic pH as well as first pass metabolism to carry optimum amount of drugs to target tissues. Being smaller in size nano carriers also provides rapid onset of actions [ 34 ].

For delivery of drug by using novel drug delivery system, herbal drugs present themselves as potential candidate because of following reasons: The side effects that are seen with other drugs are absent with natural compounds. Natural compounds have traditional backing for their action and safety potential whereas modern medicines are more toxic even if they are experimentally proven for their action [ 35 ].

The major benefit provided by novel drug delivery system is to elicit better therapeutic response with minimum doses. Types of carriers used for herbal drug delivery and synthetic drugs are as follows:.

Phytosomes contains lipid soluble complex of phospholipids and phyto-constituents. Some literatures also referred Phytosomes as ribosome [ 36 ]. Green tea phytosomes, Ginkgo biloba phytosomes, Centella phytosomes, Meriva phytosome, Zanthalene phytosomes, Sericoside phytosomes are some examples of phytosomes which are recently developed and characterized for different ailments.

Among all of them Zanthalene phytosomes are prepared especially for the treatment of fungal disease. Advantages of Phytosomes Phytosomes are not degraded by bacteria or digestive secretion of guts.

It has better stability because of the formation of bonds chemically connecting phytoconstituents and phosphatidylcholine molecules. Phytosomes delivers herbal drug to the respective target tissues [ 37 ].

It shows greater therapeutic benefit due to better absorption of lipid insoluble polar phytoconstituents in turn shows better bioavailability [ 38 ].

Liposomes contain microscopic vesicles made up of lipid bilayer arranged in concentric fashion and the separation is filled with aqueous medium.

Lipophilic substances are inserted into the lipid bilayer whereas aqueous compartment traps hydrophilic substance.

Liposomes show better bioavailability, stability and enhanced pharmacokinetic property [ 39 ]. There are various herbal and synthetic liposomes are prepared for the effective treatment of different skin diseases.

In , a herbal liposomal gel containing ketoconazole and neem extract was developed for the effective treatment of seborrheic dermatitis against Aspergillus niger and Candida albicans. The results indicated that developed liposomal gel have great potential and showed synergetic effect for the treatment.

Advantages of liposomes Liposome formulation is better options for producing sustained release formulations as it enhances drug solubility.

It is easy to load phytoconstituents of any chemical nature whether it is hydrophilic, amphiphilic or lipophilic [ 40 ]. This carrier system has particle size within the range between 1 and nm. The particles which are of nano size are made up of polymer of synthetic or semisynthetic origin.

Nanoparticles are microencapsulated to protect them from any kind of losses. Nanoparticles were made to encounter the problem of solubility and toxicity associated with triptolide [ 41 ]. Advantages of herbal nanoparticle delivery system: Nanoparticles having smaller size shows better dissolution in turn enhances solubility of dosage form and it also delivers drug with specificity thereby enhancing the efficacy [ 42 ].

In this drug delivery system inner phase stores the drugs and because of its contact with tissue directly drug release is slow. As per few reports oil of Pterodon emarginatus are considered to have property to enhance anti-inflammatory activity [ 43 ]. Formulation, development and evaluation of microemulsion gel of hydroalcoholic extract of Quercus infectoria in the treatment of different skin ailments was successfully prepared.

Tannins which are prime constituent of galls can be effectively treat different skin conditions. This drug delivery system have matrix and the drug is dispersed in a polymer which are present inside this matrix.

Particle size that can be used is in between 1 and μm. The release of drug is dependent on the dissolution and degradation rate of the said matrix. Release of drug occurs according to first order kinetic.

For example, development and evaluation of floating microspheres of curcumin prepared by emulsion solvent diffusion method for treatment of onychomycosis. The result shows improved absorption kinetics of curcumin. Advantages of microsphere formulations The major advantage of this kind of formulation is that it taken orally or parentally and their site of release can also be targeted [ 44 ].

Niosomes are similar as liposomes bjt are far more stable than liposomes. Niosomes are made up of surfactant like dialkyl polyglycerol which is noninonic in nature and are able encapsulate variety of drugs. Niosomes are more economical than liposomes [ 32 ].

Chitosan niosomal gel, miconazole niosomes are prepared as an effective nanocarrier against both dermatophytes and yeasts. In this system of drug delivery, patches encapsulating drugs are prepared and are placed on the skin. Through the skin drug enters into the blood vessels. This system is beneficial when the required effect of oral therapy was not found to be up to the mark.

Patches of antismoking and anti-motion sickness are available in market [ 45 ]. Advantages of transdermal drug delivery The transdermal delivery system has advantages such as it provides enhanced bioavailability and provides a better alternative of dosage form for unconscious or vomiting patients [ 46 ].

Ethosomes are composed of phospholipids and ethanol and are in the form of sac. Ethanol present in ethosomes acts as permeability enhancer. Ethosomes are found in the form of cream and gel for better patient compliance [ 47 ]. Now a days, Transethosomes and Nanoethosomes used most widely which are the advanced type of ethosomes having edge activator in it.

These advanced novel carrier system is much better than conventional novel carriers like transferosomes and liposomes [ 48 ]. Clotrimazole, Itraconazole, Miconazole are synthetic drugs which are prepared and evaluated successfully for the treatment of dermatophytosis or ringworm.

Tridax procumbens and Galinsoga parvifolia are two herbs used into ethosomal gel against Trichophyton species. Advantages of Ethosome Ethosomes can entrap all type of drugs and have better skin permeability [ 46 ].

Transferosomes contains phospholipids sac which behaves as carrier for delivery of drug through the skin. As Transferosomes are flexible in nature they cross the skin through the intracellular space found within the skin.

Transferosomes of Colchicines shows lesser side effect than its oral form [ 49 ]. Advantages of Transferosomes: Transferosomes being flexible can pass through narrow openings of skin.

The problem associated with herbal drug formulation is their solubility. To counter this solubility problem, complex formation is done which gives particulates with well-defined stoichiometry. Few commonly used complexing agents are EDTA and cyclodextrin [ 51 ].

The hydrogel are three dimensional structures with cross linking of polymers. As name suggest hydrogels are hydrophilic in nature. Hydrogels can be designed into different forms according to the needs.

The form can be of slabs, films and nanoparticle coating [ 52 ]. Hydrogels have the potential to bind both herbal as well as synthetic drug, this ability can be treated as avenue for further research [ 53 ].

There are many marketed formulation of novel drug delivery available in the market [ 46 , 54 ] Here are list of some novel carriers used with their plant components or synthetic drugs combinations for different fungal infections Table 5. List of some novel carriers for antifungal plant components and synthetic drugs [ 55 ].

The last 20 years has shown an increase in number of fungal infection. Currently used drugs in treatment of fungal infection are having many side effects, and development of resistance is very common against these drugs.

Plants have been considered as traditional source of antifungal medicines for past many years. Plant bioactive with antifungal activity can be considered as an option for development of new and improved alternative formulations in antifungal therapy.

Development of improved formulations with plant phytcompounds is the need of the hour for efficient treatment of fungal diseases. Further research on this field can provide us with increased number of options in treatment of fungal diseases that will give the patients with a better quality of life.

Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Edited by Bassam Hassan. Open access peer-reviewed chapter Medicinal Plants Having Antifungal Properties Written By Koushlesh Kumar Mishra, Chanchal Deep Kaur, Anil Kumar Sahu, Rajnikant Panik, Pankaj Kashyap, Saraswati Prasad Mishra and Shweta Dutta.

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Impact of this chapter. Abstract In the past few decades, a worldwide increase in the incidence of fungal infections has been observed as well as rise in the resistance of some species of fungi to different fungicidal used in medicinal practice. Keywords antifungal phytocompounds fungicidal antifungal therapy fungal infections.

Introduction to fungal disease Fungal infections are one of the most deadly infections accounting in excess of 1. No Class Drugs Uses 1.

Azole antifungals Clotrimazole, Econazole, Isoconazole, Miconazole, Ketoconazole, Itraconazole Topical fungal infections, Candidiasis, aspergillus and candida infections, vaginal yeast infections 2.

Echinocandins Caspofungin, Micafungin Esophageal Candidiasis, Salvage therapy 4. Polyenes Amphotericin B, Nystatin Systemic mycosis, superficial mycosis 5.

Phenolic cyclohexane Griseofulvin Dermatophytic infections 6. Synthetic pyrimidines Flucytosine Cryptococcosis, severe invasive aspergillosis, cryptococcal meningitis treated along with other antifungals 7.

Morpholines Amorolfine Topical fungal infections 8. Pyridines Buthiobate, Pyrifenox Dermatophytic infections, Tinea conditions 9. Phthalimides Captan Invasive dermatophytic conditions and candida infections.

Table 1. No Side effects Drugs 1. Non-melanoma skin cancer prolonged therapy Voriconazole 2. Fever, Chills Isavuconazole, Ketoconazole, Voriconazole, Flucytosine, Anidulafungin, Caspofungin 3.

Rash Flucytosine, Fluconazole, Ketoconazole, Clotrimazole, Voriconazole 4. Nausea, vomiting Isavuconazole, Itraconazole, Flucytosine, Fluconazole, Ketoconazole, Clotrimazole, Voriconazole 5. Abdominal pain Flucytosine, Ketoconazole, Isavuconazole, Voriconazole 6. Anemia Amphotericin B, Caspofungin, Flucytosine 7.

Leukopenia, Thrombocytopenia Flucytosine, Fluconazole 8. Decreased renal function Amphotericin B, Caspofungin, Voriconazole 9. Headache Flucytosine, Fluconazole, Ketoconazole, Isavuconazole, Voriconazole, Caspofungin Dark urine, clay-colored stools, jaundice Anidulafungin C, Micafungin.

Table 2. Adverse side effects of different antifungals. Botanical name Family Parts used Chemical classes Microorganism tested 1. Eugenia uniflora Myrtaceae Leaves Sesquiterpenes, Monoterpene, hydrocarbons C.

albicans, C. dubliniensis, C. glabrata, C. krusei [ 17 ] 2. Psidium guajava Myrtaceae Leaves Methanolic extract C. krusei [ 17 ] 3. Curcuma longa Zingiberaceae Rhizome Turmeric oil C.

krusei [ 17 ] 4. Piptadenia colubrina Mimosaceae Stem bark — C. glabrata [ 17 ] 5. Schinus terebinthifolius Anacardiaceae Stem bark Extract C. dubliniensis [ 17 ] 6. Persea americana Lauraceae Leaves Chromene C. albicans C. dubliniensis C. krusei [ 17 ] 7.

Parapiptadenia rigida Fabaceae Stem bark Pyrrolidine amide C. albicans [ 17 ] 8. Ajania fruticulosa Asteraceae Fruits Guaianolides Candida albicans, C. glabrata A. fumigatus [ 17 ] 9. Alibertia macrophylla Rubiaceae Leaves Extract Cladosporium sphaerospermum; C.

cladosporioides; A. niger; Colletotrichum gloeosporioides [ 17 ] Aniba panurensis Lauraceae Whole plant — C. albicans [ 17 ] Aquilegia vulgaris Ranunculaceae Leaves and stems Bis benzyl A.

niger [ 17 ] Mimosa tenuiflora Mimosaceae Stem bark Sesquiterpene lactone C. krusei [ 17 ] regnellii Piperaceae Leaves Extract Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis [ 18 ] Rubia tinctorum Rubiaceae Root Triterpene A.

niger, Alternaria alternaria, P. verrucosum, Mucor mucedo [ 19 ] Tithonia diversifolia Asteraceae Whole plant Contained saponins, Polyphenols Microbotryum violaceum, Chlorella fusca [ 20 ] Vernonanthura tweedieana Asteraceae Root Extracts T.

mentagrophytes [ 21 ] Zingiber officinale Zingiberaceae Rhizomes Steroidal saponin P. oryzae [ 22 ] Datura metel Solanaceae Whole plant Diterpenoid, Alkaloids C. tropicalis [ 23 ] Lupinus albus Leguminosae Leaf surface — T.

mentagrophytes [ 24 ] Ecballium elaterium Cucurbitaceae Fruit Extract Boitylis cinerea [ 25 ] Cassia tora Leguminosae Seeds Anthraquinone Botrytis cinerea, Erysiphe graminis, Phytophthora infestans, Puccinia recondita, Pyricularia grisea [ 26 ] Chamaecyparis pisifera Cupressaceae Leaves and Twigs Isoflavone P.

oryzae [ 27 ] Prunus yedoensis Rosaceae Leaves Diterpenes C. herbarum [ 28 ]. Table 3. List of plants having antifungal activity against pathogenic fungi. No Plants Plant part Phytochemicals 1 Aegle marmelos Leaves Essential oils 2 Alpinia galangal Seeds Diterpenes 3 Ananas comosus Leaves Protein 4 Blumea balsamifera Leaves Flavonoid luteolin 5 Camptotheca acuminate Leaves Flavonoid 6 Capsicum frutescens Whole plant Triterpene saponin 7 Cassia tora Whole plant Emodin, physcion and rhein 8 Datura metel Whole plant Alkaloid 9 Euonymus europaeus Leaves Protein 10 Haloxylon salicornium Aerial part Alkaloid 11 Juniperus communis Leaves Essential oil 12 Khaya ivorensis Stem bark Triterpenes 13 Lycium chinense Root bark Phenolic compounds 14 Musa acuminate Banana Protein 15 Ocimum gratissimum Bark Essential oil 16 Pinus pinaster Leaves Pinosylvin 17 Polygonum punctatum Whole plant Sesquiterpene 18 Smilax medica Root Saponins 19 Solanum tuberosum Tubers Protein 20 Thymus vulgaris Whole plant Essential oil 21 Trachyspermum ammi Leaves, flowers Essential oil 22 Trigonella graecum Whole plants Peptides 23 Zingiber officinalis Rhizome Protein.

Table 4. Types of carriers used for herbal drug delivery and synthetic drugs are as follows: 4. Clotrimazole, Econazole nitrate, Fluconazole Micelles Superficial fungal infection Trichophyton sp.

Miconazole Solid lipid nanoparticles and nanostructured lipid carriers Candidiasis Candida albicans Fluconazole, Ketoconazole, Itraconazole, Voriconazole, Econazole Microemulsion Tinea corporis, Tinea circinata, Tinea pedis Candida albicans Amphotericin B Microemulsion Invasive fungal infection Trichophyton rubrum Griseofulvin Microemulsion gel Dermatophytosis Trichophyton sp.

Terbinafine Hcl Niosomes Fungal infection Aspergillus niger Griseofulvin, Amphotericin B Transferosomes Dermatophytosis Trichophyton rubrum Clotrimazole, Econazole Ethosomes Localized skin fungal infection Candida sp. Table 5. References 1. Sanglard D. Clinical relevance of mechanisms of antifungal drug resistance in yeasts Importancia clínica de los mecanismos de resistencia a los antifúngicos en levaduras.

Enfermedades Infecciosasy Microbiología Clínica. Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, et al. The global burden of skin disease in An analysis of the prevalence and impact of skin conditions. The Journal of Investigative Dermatology.

DOI: Arif T, Bhosale JD, Kumar N, Mandal TK, Bendre RS, Lavekar GS, et al. Natural products—antifungal agents derived from plants. Journal of Asian Natural Products Research. Fischer MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCrwa SL, et al. Emerging fungal threats to animal, plant and ecosystem health.

Resistance and tolerance mechanisms to antifungal drugs in fungal pathogens. Rodriguez-Tudela JL, Alcazar-Fuoli L, Cuesta I, Alastruey-Izquierdo A, Monzon A, Mellado E, et al. Clinical relevance of resistance to antifungals. International Journal of Antimicrobial Agents.

Manavathu EK, Vazquez JA, Chandrasekhar PH. Reduced susceptibility in laboratory-selected mutants of Aspergillus fumigatus to itraconazole due to decreased intracellular accumulation of the antifungal agent. Resistance of human fungal pathogens to antifungal drugs. Current Opinion in Microbiology.

Pfaller MA, Casatanheira M, Messer SA, Moet GJ, Jones RN. Diagnostic Microbiology and Infectious Disease. Odds FC. Resistance of clinically important yeasts to antifungal agents. Clinical relevance of mechanisms of antifungal drug resistance in yeasts.

Odda FC. Beck-Sague C, Banerjee S, Jarvis WR. American Journal of Public Health. Tripathi KD. Essentials of Medical Pharmacology. New Delhi, India: Jaypee Brothers Medical Publishers P Ltd.

Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrobial Agents and Chemotherapy. Revankar SJ.

Wayne State University School of Medicine, Merck Manual professional version, Antifungal drugs; Kobayashi GS. Chapter 74, disease mechanism of fungi. In: Baron S, editor. Medical Microbiology. The University of Texas Medical Branch at Galveston.

Ferreira MRA, Santiago RR, Langassner SMZ, de Mello JCP, Svidzinski TIE, Soares LAL. Antifungal activity of medicinal plants from northeastern Brazil. The danger of fungal infection is significantly elevated when the immune system is compromised by viral infection e. Risks are also elevated when natural barriers are disrupted e.

are caused by 5 candida species C. albicans , C. glabrata , C. parapsilosis , C. tropicalis , and C. albicans is the leading cause of candida infection in the U. US CDC website b. Pfaller and Diekema, ; McCarty and Pappas In addition, there has also been a steady increase in fungal drug resistance Roemer and Krysan, The broad use of antifungal agents in the agrochemical sector has also been linked to the development of cross-resistance to antifungal agents used in medicine Snelders et al.

Drug resistance is increasingly problematic with C. albicans as well as non-albicans Candida species such as C. glabrata Vallabhaneni et al. Fungal infections are typically treated with medications from one of four class of antifungal agents; polyenes, echinocandins, polyenes, and azoles Griffith et al.

In Chlormidazole 1 Figure 1 became the first clinically available azole antifungal agent, and in , Janssen Pharmaceuticals received U. Food and Drug Administration FDA approval for the first orally available antifungal agent, ± -Ketoconazole 2 Figure 1.

This led the FDA to severely restricted oral use of ± -Ketoconazole 2 in FDA Website, FIGURE 1. Structures of Chlormidazole 1 , ± -Ketoconazole 2 , and 2S, 4R -Ketoconazole sulfonamide analogs 3.

As part of our effort to address the need for new antifungal agents, we have been studying the chemical space surround ± -Ketoconazole 2. We were surprised to discover that since its initial discovery Backx et al.

In , D. Rotstein et al. They found that 2S, 4R -Ketoconazole was the most potent inhibitor of the four Rotstein et al. Separately, we have reported on the synthesis and evaluation of a series of 2S, 4R -Ketoconazole sulfonamide analogs 3 Figure 1 as potential treatments for metabolic syndrome Blass et al.

Herein, we report the in vitro antifungal properties of these compounds against C. albicans and C. Chemical compounds: The 2S, 4R -Ketoconazole sulfonamide analogs were prepared according to our previously reported methods Blass et al.

Amphotercin B was purchased from ACTGene Inc. Catalog number R g. Catalog number QA g. Broth microdilution susceptibility test: The minimum inhibitory concentrations MIC 75 were determined by the broth microdilution method according to the Clinical and Laboratory Standards Institute CLSI MA4 standard CLSI, Briefly, a suspension of C.

albicans or C. The resuspended culture was further incubated with μl of two-fold serially diluted test compounds —0. Positive and negative control wells without antifungal agents and wells without yeast were conducted.

Increased optical density OD corresponds to the Candida growth and was quantified by comparison with untreated Candida control samples. The MIC 75 of test compounds was determined visually and spectrophotometrically OD after h.

Experiments were run in triplicate, and data was reported as a mean. Cyp3A4 inhibition assay: Human Cyp3A4 Inhibition assay: An IC 50 for inhibition human Cyp3A4 metabolism of midazolam to 1-OH-midazolam was determined with 10 concentrations of test compounds half-log serial dilutions; duplicate points.

Assays were conducted in 1 ml 96 well polypropylene plates containing µL of mM potassium phosphate pH 7. All components except NADPH were added to a prewarmed plate and reactions were initiated by adding NADPH. After 30 min at 37°C, reactions were terminated with µL acetonitrile containing 30 µM prednisone.

After centrifugation for 10 min at x g, µL of supernatants were transferred to analysis plate. The in vitro antifungal activity of our of 2S, 4R -Ketoconazole sulfonamide analogs 3a — 3l against C.

glabrata is described in Table 1. Replacing the acetamide of 2S, 4R -Ketoconazole 4 with small, linear suflonamides 3a - 3c produced compounds whose in vitro potency against the test fungi was maintained C.

Insertion of a branch point as seen in the isopropyl analog 3d , however, led to a complete loss of in vitro antifungal activity. Constraining the branch point through the formation of the corresponding cyclopropane ring 3e restore in vitro antifungal activity against both species C.

Insertion of an additional methylene unit between the cyclopropane ring and the sulfonamide moiety 3f produced a significant loss in vitro activity against C. TABLE 1. In vitro antifungal activity of 3a — 3l against C. The addition of polar groups to the sulfonamide moiety produced mixed results.

Appending a cyano group on the sulfonamide moiety 3g provided a compound with in vitro antifungal activity comparable to that of ± -Ketoconazole 2 C. Fluorination of the small, linear sulfonamides produced some surprising results.

The CF 3 analog 3i was less potent C. Similar results were observed when the ethyl sulfonamide and n-propyl sulfonamide where capped with a CF 3 moiety 3j C. glabrata no effect. Interestingly, capping the ethyl sulfonamide with a difluoro unit 3l , however, produced a significant increase in vitro antifungal activity against both species examined C.

Importantly, the in vitro antifungal activity of 3l exceeded that of both Amphotericin B and ± -Ketoconazole against C.

We also determined the capacity of our compounds to inhibit human Cyp3A4. As noted above, C. glabrata are responsible for a large portion of Candida infection in the US and represent a serious health threat US CDC website, a. Blood stream infection of either of these organisms are associated with high mortality Timmermans et al.

Immunocompromised patients are at an even greater risk should they be unfortunate enough to experience infections with C. albicans, C. glabrata, or other candida species Monk et al.

In addition, the rise of drug resistant fungi Sanglard et al. Similar to antibiotics and antimicrobial agents, the appearance of clinically relevant drug resistant fungi has been driven by prolonged use of antifungal agent in clinical setting as well as in the agricultural sector Snelders et al.

Our studies focused on the further exploration of the chemical space surrounding ± -Ketoconazole 2 began with the observation that the initial disclosure of this antifungal agent Beckx described only a handful of analogs. This initial disclosure predates the advent of both high through put chemistry and high throughput screening, which may explain the limited nature of the original disclosure.

Surprisingly, we found that the literature contained very few additional disclosures of ± -Ketoconazole analogs, and we viewed this as an opportunity to explore the chemical space surrounding this antifungal agent.

Specifically, we have demonstrated that the acetamide of 2S, 4R -Ketoconazole 4 can be replaced with sulfonamides 3a - 3l to produce compounds that have in vitro antifungal properties with respect to C. Interestingly, we noted a divergence between antifungal activity and Cyp3A4 inhibition, Specifically, we observed that our most potent in vitro antifungal agent 3l demonstrated a wider window between Cyp3A4 inhibition and its activity against C.

albicans than ± -Ketoconazole 2 2. Additional studies will be required to determine the true potential of this opportunity. BB was responsible for designing the compounds, developing the necessary synthetic methods and preparing some of the 2S, 4R -ketoconazole sulfonamide analogs.

He also co-mentored BD as he prepared additional compounds. oversaw the effort of RS as he executed the in vitro antifungal assay described herein. RS executed the in vitro antifungal assays described herein. BD was responsible for preparing some of the 2S, 4R -ketoconazole sulfonamide analogs.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Backx, L. Dioxolanylmethyl -1H-1, 2, 4-triazoles, US patent application USA U.

Trademark Office , 1. Google Scholar. Blass, B. Design, synthesis, and evaluation of 2S, 4R -Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome. PubMed Abstract CrossRef Full Text Google Scholar.