Synthesis and Antimalarial Activity of 7-Chloro-4-(4-(2-(Oxo, Hydroxyl & Fluoro-2-1 (4-Phenyl)Ethyl)Piperazin-1-yl)Quinoline Derivatives

Since these days, microbes are resistant to the drugs available in the market, which has caused an alarming impact on society. 18 compounds in a series of 7-chloro-4-(piperazin-1-yl)quinoline derivatives were synthesized by nucleophilic addition reaction of piperazine with 4,7-dichloroquinoline followed by phenacyl bromides addition to heteroaryl piperazine and then reduction and fluorination. All 18 compounds were evaluated in vitro for their antimalarial activity against plasmodium falciparum strain. Although 12 compounds showed good activity, compound 3c was found to be more potent than standard drug Quinine having MIC 0.18 μg/ mL. On the other hand, 3d, 3e, 5a, and 5f were found to be equipotent (MIC 0.26 μg/ mL) to the standard drug.

In Vitro Antimalarial Activity and Toxicity of Helianthus annuus L. Leaf Extract against Plasmodium falciparum

Background: Malaria is one of the public health problems in Indonesia. The morbidity rate is still quite high, especially in the eastern part of Indonesia. Objective: This study aimed to determine the inhibitory activity of the leaf extracts of Helianthus annuus L. against Plasmodium falciparum strain 3D7 as well as the cytotoxicity of the extracts. Methods: The leaves of H. annuus were extracted by the maceration method with n-hexane, chloroform, and ethanol 96% to increase polarity. The antimalarial assay was performed by using Trager and Jensen method, and the cytotoxicity test was carried out by the MTT method. Results: The results of antimalarial study showed that the chloroform extract had IC50 value of 0.002 µg/mL and CC50value of 138.03 µg/mL, 96% ethanol extract had an IC50 value of 0.02 µg/mL and CC50 value of 617.81 µg/mL, and n-hexane extract had an IC50 value of 1.29 µg/mL and CC50 value of 104.89 µg/mL. The selectivity index (SI) values of the chloroform, ethanolic, and n-hexane extracts were calculated and obtained 69,015.00, 30,890.50, and 81.31, respectively. Conclusion: To conclude, the chloroform extract of H. annuus L. leaf gave strong antimalarial activity against P. falciparum strain 3D7 without any cytotoxicity; therefore, H. annuus L. leaf can be a good candidate for the development of an antimalarial drug.

Biological Activity Evaluation and In Silico Studies of Polyprenylated Benzophenones from Garcinia celebica

This study aimed to isolate polyprenylated benzophenones from the rootbark of Garcinia celebica and assess their activities in vitro and in silico. The antioxidant activity was evaluated by the DPPH, ABTS, and FRAP methods. The cytotoxicity was evaluated against HeLa, MCF-7, A549, and B16 cancer cell lines. The antiplasmodial activity was performed against the chloroquine-sensitive Plasmodium falciparum strain 3D7. Molecular docking was analyzed on alpha-estrogen receptor (3ERT) and P. falciparum lactate dehydrogenase enzyme (1CET). The prediction of ADMET for the compounds was also studied. For the first time, (-)-cycloxanthochymol, isoxanthochymol, and xanthochymol were isolated from the root bark of Garcinia celebica. The antioxidant and cytotoxicity evaluation showed that all benzophenones exhibited antioxidant activity compared to gallic acid and quercetin as positive controls and also exhibited strong activity against HeLa, MCF-7, A549, and B16 cell lines compared to cisplatin as the positive control. The antiplasmodial evaluation showed that isoxanthochymol exhibited activity against the chloroquine-sensitive P. falciparum strain 3D7. In addition, the in silico molecular docking study supported in vitro activities. The ADMET analysis also indicated the isolated benzophenones are potential oral drug candidates.

A Novel Trimeric Triterpene From Chisocheton ceramicusMiq.

A novel trimeric triterpene, bismoronic ceramicine (1), was isolated from the bark of Chisocheton ceramicus Miq. The structure was elucidated based on spectroscopic data and chemical correlations. Bismoronic ceramicine (1) showed moderate antimalarial activity against Plasmodium falciparum strain 3D7.

Antiplasmodial activity of faloak bark (Sterculia quadrifida, R.Br.) extract from East Nusa Tenggara, Indonesia

The current development of antimalarial drug resistance encourages researchers to discover and develop novel antimalarials. One of its alternatives for antimalarial discovery is using medicinal plants remembering the success of artemisinin. Sterculia quardrifida R. Br. bark, locally name as faloak, is an endemic medicinal plant from East Nusa Tenggara that has been used traditionally to treat malaria. However, its antimalarial activity has not been investigated, yet. This study was aimed to evaluate the antiplasmodial activity of ethanolic extract of faloak bark against Plasmodium falciparum in vitro. Using FCR-3 P. falciparum strain, the ethanolic extract was evaluated on various concentration (1, 10, 50, and 100 μg/mL, respectively). The IC50 value was determined by the relationship between concentration and percentage of growth inhibition. The result showed that the percentage of inhibition of P. falciparum was concentration dependent, higher concentration resulting on higher percentage of inhibition with the IC50 42.399 ± 9.517 μg/mL. It can be concluded that the ethanolic extract of faloak bark have moderate antiplasmodial activity against P. falciparum in vitro.

Penurunan Laktat Dehidrogenase Plasmodium falciparum strain D10 pada pemberian Fraksi Tithonia diversifolia (Hemsley)

Penelitian terdahulu menunjukkan bahwa fraksi ke-6 (F6) merupakan fraksi aktif (F-akt) daun Tithonia diversifolia (Hemsley) A.Gray yang menghambat pertumbuhan Plasmodium. Pertumbuhan parasit ini memerlukan energi yang diperoleh dari aktivitas laktat dehidrogenase (LDH). Penelitian ini bertujuan mengkaji aktivitas antiplasmodium fraksi aktif T. diversifolia terhadap kadar LDH kultur P. falciparum. Kultur Plasmodium falciparum strain D10 stadium cincin dibagi menjadi kelompok eritrosit tidak terinfeksi (KTI), eritrosit terinfeksi (KI), dan eritrosit terinfeksi Plasmodium yang diberi F6 (F-akt) T. diversifolia (KI+F-akt) konsentrasi 9,38-150 µg/mL. Kultur diinkubasi 48 jam. Media kultur diukur kadar LDH-nya secara enzimatik. Adanya perbedaan LDH antar kelompok dianalisa dengan Anova. Penghambatan aktivitas LDH (IC50) ditetapkan dengan analisa probit. Kadar LDH kelompok KI (362,33 ± 133,18 U/L) lebih tinggi daripada KTI (270,33 ± 65,85 U/L) (p>0,05). Pemberian F-akt pada KI menyebabkan kadar LDH parasit lebih rendah daripada KI. Kadar LDH parasit yang diberi F-akt konsentrasi 9,38; 18,75; 37,50; dan 150 µg/mL secara berturut-turut adalah 365,5 ± 129,5; 210,5 ± 1,5; 195,5 ± 81,5; dan 111,5 ± 53,5 U/L. Tidak ada perbedaan kadar LDH antar kelompok penelitian (p>0,05). F-akt T. diversifolia mampu menghambat LDH P. falciparum strain D10 dengan nilai IC50 = 39,22 µg/mL.Kata kunci: Tithonia diversifolia, laktat dehidrogenase, Plasmodium falciparum

Two in one: bifunctional derivatives of trolox acting as antimalarial and antioxidant agents

Background: The aim of the present work was to set-up compounds that are able to act simultaneously as antimalarial and antioxidants. Trolox, a known antioxidant was chosen as a core structure to ensure the antioxidant activity and contribute to antiplasmodial effect. Results: Ten compounds were prepared in one step and evaluated on chloroquino-sensitive (3D7) and chloroquino-resistant (FcB1) strains of Plasmodium falciparum. The most active compound (3d) shows antiplasmodial activity in the range of chloroquine against chloroquino-sensitive and chloroquino-resistant P. falciparum strain. The antioxidant activity of (3d) was conducted through four tests and was found to be more potent than trolox itself and L-ascorbic acid. Conclusion: Compound (3d) can be considered as an excellent lead molecule for further in vivo studies. This study paves the way for building large chemical libraries to be investigated in the field of malaria.

Synthesis and Antiplasmodial Evaluation of 4-Carboxamido- and 4-Alkoxy-2-Trichloromethyl Quinazolines

From three previously identified antiplasmodial hit compounds (A–C) and inactive series (D), all based on a 2-trichloromethylquinazoline scaffold, we conducted a structure-activity relationship (SAR) study at position four of the quinazoline ring by synthesizing 42 novel derivatives bearing either a carboxamido- or an alkoxy-group, to identify antiplasmodial compounds and to enrich the knowledge about the 2-trichloromethylquinazoline antiplasmodial pharmacophore. All compounds were evaluated in vitro for their cytotoxicity towards the HepG2 cell line and their activity against the multiresistant K1 P. falciparum strain, using doxorubicin, chloroquine and doxycycline as reference drugs. Four hit-compounds (EC50 K1 P. falciparum ≤ 2 µM and SI ≥ 20) were identified among 4-carboxamido derivatives (2, 9, 16, and 24) and two among 4-alkoxy derivatives (41 and 44). Regarding the two most potent molecules (16 and 41), five derivatives without a 2-CCl3 group were prepared, evaluated, and appeared totally inactive (EC50 > 50 µM), showing that the 2-trichloromethyl group was mandatory for the antiplasmodial activity.

BIOAKTIVITAS ANTIMALARIA EKSTRAK METANOL SPONS Petrosia ficiformis ASAL TANJUNG RUM TIDORE KEPULAUAN

Malaria adalah masalah kesehatan serius disebabkan parasit Plasmodium falciparum telah resisten (kebal) terhadap obat antimalaria yang ada seperti chloroquin. Obat baru dengan struktur molekul dan mekanisme aksi yang unik sangat diperlukan untuk menggantikan obat-obat yang telah reisten. Uji bioaktivitas antimalaria ekstrak metanol spons P. ficiformis telah dilakukan terhadap parasit Plasmodium falciparum strain 3D7. Ekstrak spons diperoleh dengan metode maserasi menggunakan pelarut metanol dan uji aktivitas antimalarial menggunakan metode in-vitro dengan variasi konsentrasi ekstrak 0,01, 0,1, 1, 10, dan 100 µg/mL. Hasil penelitian menunjukkan bahwa ekstrak metanol spons P. ficiformis sangat efektif menghambat pertumbuhan parasit malaria dengan nilai IC50 = 20,489 µg/mL.