DDD01035881
DDD01035881 is a Plasmodium falciparum Pfs16 inhibitor, with an EC50 of 130 nM for exflagellation of male gametes of Plasmodium falciparum NF54 gametocytes. DDD01035881 stabilizes mature activated male gametocyte Pfs16, mimics the Pfs16-deficient phenotype, blocks the early formation process of male gametes before DNA replication, inhibits exflagellation, and exhibits male-specific activity with no activity against female gametes or asexual malaria parasite stages. DDD01035881 can be used in malaria-related research.
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- No. CAS: 1396858-56-2
- Fòrmula: C14H14BrNO4S2
- Peso molecular:404.30
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
In Vitro
Racemic DDD01035881 (compound 3) (40 nM - 25 μM; no preincubation; immediate activation of gamete formation) potently inhibits male gamete exflagellation in Plasmodium falciparum NF54 gametocytes with an EC50 of 130 nM, with the (−)-enantiomer being the active form, exhibiting an EC50 of 46 nM[1].
DDD01035881 (2-10 µM; 24-48 h) potently inhibits Plasmodium falciparum male gamete formation with an IC50 of 0.19 µM and completely blocks parasite transmission to Anopheles mosquitoes in direct-mode SMFA at 10 µM[2].
DDD01035881 (10 µM; 24 h) arrests Plasmodium falciparum male gametogenesis at the rounding-up stage, preventing DNA replication and exflagellation when used at 10 µM for 24 h pre-incubation[2].
DDD01035881 (1.41×10-4-25 µM; 72 h)'s sulphonamide group is critical for its male-specific Plasmodium falciparum gamete inhibition activity, while halogenation of a benzene-substituted thiophene R′-group enhances potency, with all active analogues retaining no activity against female gametes[2].
DDD01035881 potently inhibits male gamete formation in Plasmodium falciparum NF54 stage V gametocytes with an IC50 of 292 nM[3].
DDD01035881 (100 μM) stabilises the Pfs16 protein in lysates from activated Plasmodium falciparum NF54 stage V gametocytes, confirming direct target engagement[3].
DDD01035881 (1 nM-100 μM) stabilises the Pfs16 protein in lysates from activated Plasmodium falciparum NF54 stage V gametocytes in a concentration-dependent manner[3].
DDD01035881 (5 μM) reversibly blocks microgametogenesis in Plasmodium falciparum NF54 stage V gametocytes within a 6-minute window post-activation[3].
DDD01035881 (25 μM) does not inhibit sexual conversion or early gametocyte development in Plasmodium falciparum Pf2004/164-tdTomato parasites[3].
DDD01035881 does not disrupt DNA replication or ploidy progression during microgametogenesis in Plasmodium falciparum PfDynGFP/P47mCherry male gametocytes[3].
DDD01035881 (10 μM; 48 h) shows no cytotoxicity against HepG2 human cells[1].
DDD01035881 (3 μM; up to 45 min) has low metabolic stability in mouse liver microsomes, with a half-life of 1.23 min and an intrinsic clearance of 1130 μL/min/mg protein[1].
DDD01035881 has favourable in vitro DMPK properties including high aqueous solubility and negligible metabolism in mouse liver microsomes[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HepG2 human cell line
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Concentration:10 μM
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Incubation Time:48 h
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Result:Showed no cytotoxicity when compared to the DMSO control.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | T1/2 |
|---|---|---|---|---|---|
| Mice[2] | 50 mg/kg | i.p. | 1582 ng/mL | 0.083 h | 90 min |
In Vivo
DDD01035881 (2 mM; topical application to dorsal thorax) causes a 40.4% reduction in P. falciparum oocyst prevalence in female Anopheles gambiae G3 mosquitoes[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:TO (Tucks Ordinary) mice (female, 6-8 weeks old); BALB/c mice (female, 6-8 weeks old)[2]
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Dosage:50 mg/kg (24h before mosquito feed; 30min before mosquito feed)
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Administration:i.p.; single dose
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Result:Showed no transmission-blocking efficacy at the oocyst level when administered 24 hours before mosquito feed.
Reduced oocyst intensity by 99.6% compared to vehicle controls when administered 30 minutes before mosquito feed.
Maintained stable plasma concentrations of ~1000 ng/mL up to 120 minutes post-dosing, with an approximate half-life of 90 minutes, a Cmax of 1582 ng/mL, and a Tmax of 0.083 hours.
Did not affect asexual parasitaemia or gametocytaemia in infected mice.
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Animal Model:G3 (female, 4-7 days old)[4]
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Dosage:2 mM
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Administration:topical application to dorsal thorax
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Result:Reduced P. falciparum oocyst prevalence by 40.4%.
Reduced median oocyst intensity from 6 in controls to 3.
Chemical Information
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No. CAS 1396858-56-2
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Peso molecular 404.30
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Fòrmula C14H14BrNO4S2
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SMILES
O=S(NCC1(C2=C(OCC1)C=CC=C2)O)(C3=CC=C(Br)S3)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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PCNA Immunodetection Proliferation Assay
PCNA immunodetection measures proliferative activity by detecting proliferating cell nuclear antigen, a nuclear protein associated with DNA polymerase δ function and DNA replication. The assay readout is the proportion of PCNA-positive nuclei among total counted cells, but PCNA labeling is not identical to BrdU labeling because PCNA can mark late G1/early S-associated replication competence and may persist beyond active DNA synthesis depending on fixation and extraction conditions.
Pureza y Documentación
Referencias
[1]. Rueda-Zubiaurre A, et al. Structure-Activity Relationship Studies of a Novel Class of Transmission Blocking Antimalarials Targeting Male Gametes. Journal of medicinal chemistry. 2020 Mar 12;63(5):2240-2262. [Content Brief]
[2]. Delves MJ, et al. A high throughput screen for next-generation leads targeting malaria parasite transmission. Nature communications. 2018 Sep 18;9(1):3805. [Content Brief]
[3]. Yahiya S, et al. A novel class of sulphonamides potently block malaria transmission by targeting a Plasmodium vacuole membrane protein. Disease models & mechanisms. 2023 Feb 01;16(2):dmm049950. [Content Brief]
[4]. Probst AS, et al. In vivo screen of Plasmodium targets for mosquito-based malaria control. Nature. 2025 Jul;643(8072):785-793. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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