antifungal compound/agent 22 (compound D16) is a potentially orally bioactive antifungal active molecule with IC50 of 0.5 μg/mL. antifungal compound/agent 22 can penetrate the BBB (blood-brain barrier) and kill C. neoformans H99 cells by destroying the integrity of the fungal cell membrane. antifungal compound/agent 22 has selective anti-cryptococcal activity, good metabolic stability and low cell toxicity/cytotoxicity.

Physicochemical Properties

CAS #	2640054-39-1
PubChem CID	163322257
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	448
Defined Atom Stereocenter Count	0
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Antifungal 22 (Compound D16) suppresses the manufacture of ergosterol (0–1 μg/mL, 24 hours), which causes stress-induced activation of ERG genes in Cryptococcus neoformans H99 [1]. Antifungal 22 (0-8 μg/mL) efficiently prevents Cryptococcus neoformans H99 from growing (0-72 hours) and also prevents C from forming. biofilm (24 hours) of Neoformans H99 in a concentration-dependent way [1]. Antifungal 22 (0-8 μg/mL, 48-72 h) has fungistatic and selective anti-cryptococcal action [1]. With an IC50 of 20.18 μM, antifungal 22 (0-100 μM, 48 hours) shown minimal cytotoxicity against human HUVEC cell lines [1].
ln Vivo	Antifungal 22 (D16) has demonstrated strong anticryptococcal efficacy (15 mg/kg intragastric once daily for 5 days) [1].
Cell Assay	Cell Proliferation Assay Cell Types: Cryptococcus neoformans H99 cells [1] Tested Concentrations: 0, 1, 2, 4, 8 μg/mL Incubation Duration: 0, 4, 8, 12, 24, 48 and 72 hrs (hours) Experimental Results: Almost Complete 8 μg/mL can inhibit the growth of Cryptococcus neoformans H99, and the inhibition rate is still close to 100% after 72 hrs (hours). The minimum bactericidal concentration is 8 μg/mL. Cell viability assay Cell Types: Fungal cells (RPMI 1640 medium) [1] Tested Concentrations: 0, 0.5, 1, 2, 4, 8 μg/mL Incubation Duration: 48, 72 hrs (hours) Experimental Results: Displayed selective anti-cryptococcal activity , the IC50 range is 0.06-2 μg/mL, and the MIC50 value (average IC50 value) is 0.62 μg/mL.
Animal Protocol	Animal/Disease Models: ICR female mice (18-22 g, 4-6 weeks, tail vein injection of Cryptococcus neoformans H99 cells) [1] Doses: 15 mg/kg Route of Administration: intragastric, one time/day for 5 days Experimental Results: Displayed potent anti-cryptococcal efficacy, Dramatically reducing the number of Cryptococcus neoformans H99 cells in the brain after 5 days and extending the median survival time of infected mice (14 days) at a dose of 15 mg/kg.
References	[1]. Li W, Yun Z, Ji C, et al. Discovery of Novel Sertraline Derivatives as Potent anti-Cryptococcus Agents.J Med Chem. 2022 Mar 6;10.1021/acs.jmedchem.1c01845.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)