Evidence map›Paper›PMID 36375338›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2022

Anti-malarial activity of HCl salt of SKM13 (SKM13-2HCl).

Thuy-Tien Thi Trinh, Su-Yeon Yun, Gum-Ju Bae, Kwonmo Moon, Hyelee Hong, Tae Hui Eum, Young-Ah Kim, Soon-Ai Kim, Hyun Park, Hak Sung Kim and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Thuy-Tien Thi TrinhDepartment of Tropical Medicine and Parasitology, Medical Research Center, Institute of Endemic Diseases, Seoul National University, Seoul, 03080, Republic of Korea.
Su-Yeon YunZoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, 460 Iksan-daero, Iksan, 54538, Republic of Korea.
Gum-Ju BaeZoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, 460 Iksan-daero, Iksan, 54538, Republic of Korea.
Kwonmo MoonCollege of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea.
Hyelee HongDepartment of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
Tae Hui EumDepartment of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
Young-Ah KimCollege of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea.
Soon-Ai KimCollege of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea.
Hyun ParkZoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, 460 Iksan-daero, Iksan, 54538, Republic of Korea. Electronic address: hyunpk@wku.ac.kr.
Hak Sung KimCollege of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea. Electronic address: hankidad@wku.ac.kr.
Seon-Ju YeoDepartment of Tropical Medicine and Parasitology, Medical Research Center, Institute of Endemic Diseases, Seoul National University, Seoul, 03080, Republic of Korea; Department of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. Electronic address: yeosj@snu.ac.kr.
Wonkwang University · KRSeoul National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malaria is among the most devastating and widespread tropical parasitic diseases in developing countries. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. We synthesized HCl salt of SKM13 (SKM13-2HCl) based on the modification of SKM13 to improve solubility in water. The anti-malarial activity of the synthesized drug was evaluated in both in vitro and in vivo models. The selective index indicated that SKM13-2HCl showed the same effectiveness with SKM13 in Plasmodium falciparum in in-vitro. Even though, in vivo mouse study demonstrated that SKM13 (20 mg/kg) at single dose could not completely inhibit P. berghei growth in blood. The survival rate increased from 33 to 90% at 15 days after infection. However, SKM13-2HCl (20 mg/kg) at a single dose increased the survival rate up to 100% at the same duration. Ultra-High-Performance Liquid Chromatography (UHPLC) showed that solubility in water of SKM13 and SKM13-2HCL was 0.389 mg/mL and 417 mg/mL, respectively. Pharmacokinetics (PK) analysis corresponded to the increased solubility of SKM13-2HCl over SKM13. Haematological parameters [red blood cell (RBC) count, haemoglobin level, and haematocrit level] supported the comparable efficacy of SKM13 and SKM13-2HCl in a 4-day suppression test. One mode of these drugs was found to be activating phosphorylation of eIF2α, hallmark of ER-stress, to kill parasite. Novel salt derivative of SKM13 (SKM13-2HCl) have enhanced anti-malarial activity against P. falciparum with endoplasmic reticulum (ER)-stress and salt form of SKM13 is an excellent direction to develop anti-malarial drug candidate in mice model.

Indexed as

AntimalarialsMalariaMalaria, FalciparumAnimalsMicePlasmodium bergheiPlasmodium falciparumWaterAntimalarialsWaterAntimalarial drugsEndoplasmic reticulum (ER)-StressMalariaPharmacokineticsSKM13-2HCl salt

Identifiers

PMID36375338
PMCPMC9771833
OpenAlexW4308579436

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.