Formulation of Cinchona Extract (Cinchona succirubra) Cream and The Safety as Hair Fertilizer

Background: cinchona extract contains quinoline alkaloids, has telangiectatic activity, is practically insoluble in water so penetration into hair follicles is low and requires a delivery system, namely cream. Objective: to determine the formula of cinchona extract cream with good activity, physical stability and safety. Methodology: cinchona bark extraction (soxhletation method), phytochemical screening, cinchona extract dosage determination, optimization of cream formula using Design Expert software version 11. Evaluation: pH, adhesion, spreadability, viscosity and cycling test stability. Activity test using guinea pigs (Cavia porcellus) for 14 days, parameters of hair length/2 days, hair mass (14th day). Acute dermal irritation test using rabbit (Orycogalus cuniculus) by erythema and edema index parameters. Results: cinchona extract (13.32% yield) contained quinoline alkaloids, cinchona extract dosage was 20% (p<0.05). The optimum formula is F2 with characteristics: pH 6.48±0.07, adhesion 1.16±0.07, spreadability 4.99±0.85 and viscosity 3067±416.45, has good physical stability. Activity test: test area hair length 13.54 – 62.14% longer than normal control and 10.10 – 49.17% than negative control. The hair mass of test area was 122.91% heavier than normal control and 104.48% of negative control (p<0.05). Cinchona extract and excipients were non-irritant. Conclusion: Cinchona extract cream (20%) has hair fertilizer activity, good physical stability and safety.

Study of Molecular Docking, Molecular Dynamic and Toxicity Prediction of Several Quinoline Alkaloid Derivatives as a Bruton Tyrosine Kinase Inhibitor as Anti-Leukemia

Quinoline alkaloid and its derivatives play a vital role in the development of new therapeutic agents. Cinnoline structure has similarities with quinoline alkaloid compound and has the potential to inhibit Bruton’s Tyrosine Kinase (BTK) in leukemia treatment. This research aims to study the interaction of several quinoline alkaloids with BTK and to predict the toxicity to ensure their safety. This study was carried out using computational studies, including molecular docking, molecular dynamics simulation, and toxicity prediction, to assess the compound’s activity towards BTK and their toxicity. Molecular docking simulations showed that ten compounds (S1, S2, S4, S5, S8, S13, S14, S16, S17, and S20) had the best affinity to BTK. Molecular dynamics simulations to these ten compounds showed that only seven compounds (S1, S5, S8, S13, S16, S17, and S20) could stabilize the interaction towards BTK with RMSD and RMSF value of 0.5 ± 2 Å and 0.5 ± 6, 5 Å, respectively. Toxicity prediction results showed that these quinoline alkaloids had various toxicity characteristics, but most were not carcinogens and mutagens (S4, S5, S6, S7, S8, S10 S11, S12, S14, and S15). It can be concluded that Yukositrin (S8) has the most potential affinity towards BTK, which can be used as anti-leukemia with low toxicity. Keywords: anti-leukemia, Bruton Tyrosine Kinase, docking, MD, quinoline alkaloids

An Overview of COVID-19 and the Potential Plant Harboured Secondary Metabolites against SARS-CoV-2: A Review

The SARS-CoV-2 virus causes COVID-19, a pandemic disease, and it is called the novel coronavirus. It belongs to the Coronaviridae family and has been plagued the world since the end of 2019. Viral infection to the lungs causes fluid filling and breathing difficulties, which leads to pneumonia. Pneumonia progresses to ARDS (Acute Respiratory Distress Syndrome), in which fluid fills the air sac and seeps from the pulmonary veins. In the current scenario, several vaccines have been used to control the pandemic worldwide. Even though vaccines are available and their effectiveness is short, it may be helpful to curb the pandemic, but long-term protection is inevitable when we look for other options. Plants have diversified components such as primary and secondary metabolites. These molecules show several activities such as anti-microbial, anti-cancer, anti-helminthic. In addition, these molecules have good binding ability to the SARS-CoV-2 virus proteins such as RdRp (RNA-dependent RNA polymerase), Mpro (Main Protease), etc. Therefore, these herbal molecules could probably be used to control the COVID-19. However, pre-requisite tests, such as cytotoxicity, in vivo, and human experimental studies, are required before plant molecules can be used as potent drugs. Plant metabolites such as alkaloids, isoquinoline ß-carboline, and quinoline alkaloids such as skimmianine, quinine, cinchonine, and dictamine are present in plants and used in a traditional medicinal system.

Antileishmanial activity of synthetic analogs of the naturally occurring quinolone alkaloid N-methyl-8-methoxyflindersin

Leishmaniasis is a neglected, parasitic tropical disease caused by an intracellular protozoan from the genus Leishmania. Quinoline alkaloids, secondary metabolites found in plants from the Rutaceae family, have antiparasitic activity against Leishmania sp. N-methyl-8-methoxyflindersin (1), isolated from the leaves of Raputia heptaphylla and also known as 7-methoxy-2,2-dimethyl-2H,5H,6H-pyran[3,2-c]quinolin-5-one, shows antiparasitic activity against Leishmania promastigotes and amastigotes. This study used in silico tools to identify synthetic quinoline alkaloids having structure similar to that of compound 1 and then tested these quinoline alkaloids for their in vitro antiparasitic activity against Leishmania (Viannia) panamensis, in vivo therapeutic response in hamsters suffering from experimental cutaneous leishmaniasis (CL), and ex vivo immunomodulatory potential in healthy donors’ human peripheral blood (monocyte)-derived macrophages (hMDMs). Compounds 1 (natural), 2 (synthetic), and 8 (synthetic) were effective against intracellular promastigotes (9.9, 3.4, and 1.6 μg/mL medial effective concentration [EC50], respectively) and amastigotes (5.07, 7.94, and 1.91 μg/mL EC50, respectively). Compound 1 increased nitric oxide production in infected hMDMs and triggered necrosis-related ultrastructural alterations in intracellular amastigotes, while compound 2 stimulated oxidative breakdown in hMDMs and caused ultrastructural alterations in the parasite 4 h posttreatment, and compound 8 failed to induce macrophage modulation but selectively induced apoptosis of infected hMDMs and alterations in the intracellular parasite ultrastructure. In addition, synthetic compounds 2 and 8 improved the health of hamsters suffering from experimental CL, without evidence of treatment-associated adverse toxic effects. Therefore, synthetic compounds 2 and 8 are potential therapeutic candidates for topical treatment of CL.

Aktivitas NADP(H) Oksidoreduktase pada Kultur Sel Kina (Cinchona ledgeriana Moens) Terelisitasi

Cinchona ledgeriana Moens is an industrial plant producing secondary metabolite quinoline alkaloids. To maintain and moreover, to increase the quinoline production especially quinine, in vitro culture system through cell culture could be a potential alternative. If the use of elicitor in cell culture can increase the production of a secondary metabolite, the activity of the enzymes involved in the biosynthetic pathway of the secondary metabolite in question might be increasing. This study aimed to examine the activity of NADPH oxidoreductase in the elicitated cell culture of C. ledgeriana and to evaluate the correlation between the activity of this enzyme and the level of quinine production. The cell cultures of Cinchona were treated with abscisic acid (ABA) or paclobutrazol (PBZ), combined with sucrose, sorbitol, or mannitol in Wood Plant (WP) media, for 7 weeks on a shaker. The quinine concentration was determined using high-performance liquid chromatography (HPLC) and the enzyme activity was measured using fluorometry. The results showed that the highest enzyme activity was found in the P7M cells (PBZ 7 mg/L + mannitol 5.3 g/L + sucrose 20 g/L), followed by the A3S cells (ABA 3 mg/L + sorbitol 5.3 g/L + sucrose 20 g/L). These results correspond to their production level of the quinine alkaloids. The lowest enzyme activity was found in the cultures without elicitor. The increase of NADP(H) enzyme activity in the P7M and A3S treatments were 13.5 and 8.5%, respectively, compared to that in the control cells. Keywords: elicitation, fluorometry, NADP(H) oxidoreductase, quinoline alkaloid