Development Of Innovative Drugs Research Articles

Methodology of the Development of a Topical Transdermal Fucoidan Delivery System

Introduction. Marine-derived polysaccharides are promising candidates for the development of innovative drugs. One of such compounds is the polysaccharide fucoidan from brown seaweeds, which shows anticoagulant and anti-inflammatory activity. The development of topical transdermal formulation for the treatment of chronic venous diseases is of particular interest, because with targeted delivery, the active compound in high concentration comes directly to the site where the drug is required, while the risk of side effects is minimal.Aim. Experimental and theoretical justification of the methodological scheme for the development of a transdermal delivery system with fucoidan for local therapy using the Quality by Design (QbD) approach.Materials and methods. Fucoidan was isolated from the thalli of Fucus vesiculosus L. from the Barents Sea according to the original technology of the MMBI RAS. All excipients were approved for medical use. The experiments for rational selection of the excipients for the transdermal delivery system (TSD) were planned using the Greek-Latin square 4 × 4 with repeated observations. The colloidal and thermal stability and pH were evaluated as physicochemical parameters of TSD Structural and mechanical properties of TSD were deter-mined with rotational viscometer. The dissolution rate of fucoidan in vitro was evaluated using the paddle-over-disk method at a temperature of 32 ± 0.5 °C.Results and discussion. The composition and technology of topical TSD цwith fucoidan were developed using the QbD concept. The composition and technology of topical TSD with 15 % of fucoidan as active ingredient were developed. TSD has thermo- and colloidal stability, and has a pH value close to the pH of human skin. Poloxamer 407 was used as a gel base; olive oil was used as a hydrophobic phase. It was found that the ratio of poloxamer 407 to the aqueous phase should be no less than 0.1 and no more than 0.37; the ratio of water to the aqueous phase should not be less than 0.56 and not more than 0.69; and the ratio of polyoxyl 40 hydrogenated castor oil to the oil phase must be at least 0.34. It was found that 9 % poloxamer 407 provides the necessary structural and mechanical properties of TSD. It has been established that the developed TSD of fucoidan with poloxamer 407 belongs to non-Newtonian flow types with plastic properties and has thixotropy.Conclusion. The complex of studies based on QbD approach led to the experimental and theoretical justification of the methodological scheme for the development of a transdermal delivery system with marine polysaccharide fucoidan. The methodological scheme takes into account the physicochemical and technological features of fucoidan and allows you to create a high-quality TSD that ensures stability and complete release of the active substance.

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an MCTS model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1

As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.

Structure modification: a successful tool for prodrug design.

Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving drug defects and optimizing the physical and chemical properties of a drug, such as lipophilicity and water solubility, changing the way of administration can be achieved through specific structural modification. Designing prodrugs by linking microenvironment-responsive groups to the prototype drugs is of great help in enhancing drug targeting. In the meantime, making connections between prodrugs and suitable drug delivery systems could realize drug loading increases, greater stability, bioavailability and drug release control. In this paper, lipidic, water-soluble, pH-responsive, redox-sensitive and enzyme-activatable prodrugs are reviewed on the basis of structural modification.

Glucotropaeolin Promotes Apoptosis by Calcium Dysregulation and Attenuates Cell Migration with FOXM1 Suppression in Pancreatic Cancer Cells.

Pancreatic ductal adenocarcinoma (PDAC) has naturally aggressive characteristics including postoperative recurrence, resistance to conventional treatment, and metastasis. Surgical resection with chemotherapeutic agents has been conducted as the major treatment for PDAC. However, surgical treatment is ineffective in the case of advanced cancer, and conventional adjuvant chemotherapy, including gemcitabine and 5-fluorouracil, show low effectiveness due to the high drug resistance of PDAC to this type of treatment. Therefore, the development of innovative therapeutic drugs is crucial to solving the present limitation of conventional drugs. Glucotropaeolin (GT) is a glucosinolate that can be isolated from the Brassicaceae family. GT has exhibited a growth-inhibitory effect against liver and colon cancer cells; however, there is no study regarding the anticancer effect of GT on PDAC. In our study, we determined the antiproliferative effect of GT in PANC-1 and MIA PaCa-2, representative of PDAC. We revealed the intracellular mechanisms underlying the anticancer effect of GT with respect to cell viability, reactive oxygen species (ROS) accumulation, alteration of mitochondrial membrane potential (MMP), calcium dysregulation, cell migration, and the induction of apoptosis. Moreover, GT regulated the signaling pathways related to anticancer in PDAC cells. Finally, the silencing of the forkhead box protein M, a key factor regulating PDAC progression, contributes to the anticancer property of GT in terms of the induction of apoptosis and cell migration. Therefore, GT may be a potential therapeutic drug against PDAC.

Roadmap for Achieving Universal Antiretroviral Treatment.

Modern antiretroviral therapy safely, potently, and durably suppresses human immunodeficiency virus (HIV) that, if left untreated, predictably causes acquired immunodeficiency syndrome (AIDS), which has been responsible for tens of millions of deaths globally since it was described in 1981. In one of the most extraordinary medical success stories in modern times, a combination of pioneering basic science, innovative drug development, and ambitious public health programming resulted in access to lifesaving, safe drugs, taken as an oral tablet daily, for most of the world. However, substantial challenges remain in the fields of prevention, timely access to diagnosis, and treatment, especially in pediatric and adolescent patients. As HIV-positive adults age, treating their comorbidities will require understanding the course of different chronic diseases complicated by HIV-related and antiretroviral toxicities and finding potential treatments. Finally, new long-acting antiretrovirals on the horizon promise exciting new options in both the prevention and treatment fields.

Current Landscape of Methods to Evaluate Antimicrobial Activity of Natural Extracts.

Natural extracts have been and continue to be used to treat a wide range of medical conditions, from infectious diseases to cancer, based on their convenience and therapeutic potential. Natural products derived from microbes, plants, and animals offer a broad variety of molecules and chemical compounds. Natural products are not only one of the most important sources for innovative drug development for animal and human health, but they are also an inspiration for synthetic biology and chemistry scientists towards the discovery of new bioactive compounds and pharmaceuticals. This is particularly relevant in the current context, where antimicrobial resistance has risen as a global health problem. Thus, efforts are being directed toward studying natural compounds' chemical composition and bioactive potential to generate drugs with better efficacy and lower toxicity than existing molecules. Currently, a wide range of methodologies are used to analyze the in vitro activity of natural extracts to determine their suitability as antimicrobial agents. Despite traditional technologies being the most employed, technological advances have contributed to the implementation of methods able to circumvent issues related to analysis capacity, time, sensitivity, and reproducibility. This review produces an updated analysis of the conventional and current methods to evaluate the antimicrobial activity of natural compounds.

Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer.

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in men in the United States. The treatment paradigm for prostate cancer has evolved with the emergence of a variety of novel therapies which have improved survival; however, treatment-related toxicities are abundant and durable responses remain rare. Immune checkpoint inhibitors have shown modest activity in a small subset of patients with prostate cancer and have not had an impact on most men with advanced disease. The discovery of prostate-specific membrane antigen (PSMA) and the understanding of its specificity to prostate cancer has identified it as an ideal tumor-associated antigen and has revived the enthusiasm for immunotherapeutics in prostate cancer. T-cell immunotherapy in the form of bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapy have shown exceptional success in treating various hematologic malignancies, and are now being tested in patients with prostate cancer with drug design centered on various target ligands including not just PSMA, but others as well including six-transmembrane epithelial antigen of the prostate 1 (STEAP1) and prostate stem cell antigen (PSCA). This summative review will focus on the data surrounding PSMA-targeting T-cell therapies. Early clinical studies with both classes of T-cell redirecting therapies have demonstrated antitumor activity; however, there are multiple challenges with this class of agents, including dose-limiting toxicity, 'on-target, off-tumor' immune-related toxicity, and difficulty in maintaining sustained immune responses within a complex and overtly immunosuppressive tumor microenvironment. Reflecting on experiences from recent trials has been key toward understanding mechanisms of immune escape and limitations in developing these drugs in prostate cancer. Newer generation BiTE and CAR T-cell constructs, either alone or as part of combination therapy, are currently under investigation with modifications in drug design to overcome these barriers. Ongoing innovation in drug development will likely foster successful implementation of T-cell immunotherapy bringing transformational change to the treatment of prostate cancer.

In situ stimulus-responsive self-assembled nanomaterials for drug delivery and disease treatment.

The individual motifs that respond to specific stimuli for the self-assembly of nanomaterials play important roles. In situ constructed nanomaterials are formed spontaneously without human intervention and have promising applications in bioscience. However, due to the complex physiological environment of the human body, designing stimulus-responsive self-assembled nanomaterials in vivo is a challenging problem for researchers. In this article, we discuss the self-assembly principles of various nanomaterials in response to the tissue microenvironment, cell membrane, and intracellular stimuli. We propose the applications and advantages of in situ self-assembly in drug delivery and disease diagnosis and treatment, with a focus on in situ self-assembly at the lesion site, especially in cancer. Additionally, we introduce the significance of introducing exogenous stimulation to construct self-assembly in vivo. Based on this foundation, we put forward the prospects and possible challenges in the field of in situ self-assembly. This review uncovers the relationship between the structure and properties of in situ self-assembled nanomaterials and provides new ideas for innovative drug molecular design and development to solve the problems in the targeted delivery and precision medicine.

Evolution of drug regulations and regulatory innovation for anticancer drugs in China.

Over the past two decades, China has introduced significant changes to drug regulations through regulatory innovations to accelerate drug review and approvals, keeping in line with the rapidly growing scientific innovation in drug research and development (R&D). In this study, we outlined the revolution of drug regulation in China since the establishment of the State Drug Administration in 1998. More particularly, we performed a comprehensive analysis of newly approved anticancer drugs in China from the year 2005 to May 2021, as a powerful illustration of how the revolution has changed the drug R&D landscape. Innovative drug development in China has boomed, benefiting in particular from pro-innovation policies as well as expedited program designations by the authority. We found a significant increase in the number of both imported and domestic new anticancer drugs from 2005 to 2021, with the emergence of drugs with novel mechanisms of action, including immune checkpoint inhibitors and cell therapy products. Drug lag has also been dramatically shortened by more than 70% for imported drugs in years 2016-2020 compared to years 2006-2010. Furthermore, we provide an insight into the potential approaches to further optimize the science-based and clinical value-based regulatory and R&D drug ecosystem in China. This review provides evidence of significant impacts of regulations and policies on drug R&D and suggests that the constantly adapting regulatory ecosystem will speed up drug development in China and worldwide.

Research progress of fibroblast growth factor in nervous system diseases.

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.

Targeting rare tumors: new focus for clinical research in China.

Rare tumor has a huge unmet medical need without standard regimens, calling for novel therapeutic interventions. The National Cancer Center of China identified a threshold of incidence for rare tumor as 2.5/100,000, based on the characteristics of Chinese population. Molecular profiles for rare tumor patients in China further provided prospects for precise and individualized targeted treatment. An ongoing phase II clinical trial, the PLATFORM study, is the first trial tailored for rare solid tumors in China, featured by molecule-guided therapeutics. With the promulgation of supportive policies to encourage the development of innovative drugs for rare tumors in China, opportunities will be provided for these patients and the gap will be filled in the treatment of rare tumors.

Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets

TWIK-related acid-sensitive K+ (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K2P) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods. They are similar to other K2P channels in that they can create and use background-leaked potassium currents to stabilize resting membrane conductance and repolarize the action potential of excitable cells. TASK channels are expressed in both the nervous system and peripheral tissues, including excitable and non-excitable cells, and are widely engaged in pathophysiological phenomena, such as respiratory stimulation, pulmonary hypertension, arrhythmia, aldosterone secretion, cancers, anesthesia, neurological disorders, glucose homeostasis, and visual sensitivity. Therefore, they are important targets for innovative drug development. In this review, we emphasized the recent advances in our understanding of the biophysical properties, gating profiles, and biological roles of TASK channels. Given the different localization ranges and biologically relevant functions of TASK-1 and TASK-3 channels, the development of compounds that selectively target TASK-1 and TASK-3 channels is also summarized based on data reported in the literature.

Accelerating the integration of China into the global development of innovative anticancer drugs.

The aim of this Policy Review was to compare China's overall and synchronous participation in clinical trials for innovative anticancer drugs with that of the USA, the EU, Japan, and South Korea, and to assess changes in the participation rate trends in these five regions. Relevant data from the top 20 international pharmaceutical companies from 2011 to 2021 were systematically collected from the Trialtrove and Pharmaprojects databases. Among the 8260 trials for 954 new anticancer drugs identified, China was involved in 8·8% of the trials and with 20·4% of the drugs being trialled. These participation rates are significantly lower than those for South Korea (14·5% of trials and 36·3% of drugs), Japan (16·1% of trials and 38·7% of drugs), the EU (40·6% of trials and 67·7% of drugs), and the USA (65·7% of trials and 91·2% of drugs; p<0·0001 for all). Similar results were found for the synchronous participation rate, defined as the proportion of drugs or trials at the highest development stage internationally, for the 803 tested drugs, which ranged from 9·0% in China to 87·7% in the USA. China's participation rate in early phase trials (4·4%) and in synchronous trials (5·4%) was even lower, in stark contrast to that of the USA (66·1% for early phase trials and 89·1% for synchronous trials). The fastest growing annual rate of participation in trials was observed in China (15·7%), followed by South Korea (8·2%) and Japan (6·8%); no change was detected in the USA or the EU. This Policy Review shows that Chinese participation in the clinical development of innovative cancer drugs by international pharmaceutical companies has increased over the past decade, but an obvious gap persists in comparison with the USA, the EU, Japan, and South Korea, especially in its synchronous participation and early participation rates.

The Potential of Industrial Agglomeration to Promote Pharmaceutical Innovation: Analysis of China's “Medicine Valley” Construction Upsurge

The Potential of Industrial Agglomeration to Promote Pharmaceutical Innovation: Analysis of China's “Medicine Valley” Construction Upsurge

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Research progress and innovation of drug delivery devices based on children's multidimensional demand for medication

Pediatric medication in China is characterized by a lack of child-specific drugs and insufficient types, specifications, dosage forms, and delivery devices. In recent years, new dosage forms with good compliance, such as inhalation preparation, rectal delivery system, and transdermal delivery system, have attracted more attention in pediatric medication. Because of the physiological characteristics of delicate viscera, difference in swallowing ability and psychological characteristics of fear of pain and aversion to bitter taste, it is particularly important to select suitable drug delivery route and drug delivery device according to children's physiological characteristics. With the help of the special drug delivery devices, traditional Chinese medicine and innovative Chinese medicine can be administered according to the expected design path, and drug delivery devices can ensure the accurate dose and improve the complia-nce to achieve the purpose of effective and safe drug delivery. It is also a way to realize the re-innovation of traditional Chinese medicine. The present study summarized the research progress in drug delivery devices for common drug delivery routes and new drug deli-very routes, put forward the innovative design idea of children's drug delivery devices according to the special needs of children, poin-ted out the compatibility of drug delivery devices and other problems in the current development, and prospected the application of intelligent information technology and additive manufacturing technology in drug delivery device innovation. This is expected to provide references for the development of innovative drugs and drug delivery devices suitable for children's multidimensional demand for medication.

Effects of traditional artiri La Li formulation on experimental models of vitiligo and mechanisms of melanogenesis

Ethnopharmacological relevanceArtiri La Li Honey Pill (ALLHP) is a traditional medicinal formula that is widely used in Xinjiang, China, for the treatment of vitiligo. Since the cause of vitiligo has not been determined, no satisfactory treatment is available. Clinical interventions include pharmacological treatment with psoralen, usually in conjunction with ultraviolet A (UVA) radiation, but toxic side effects limit this application. Studies on the activity and mechanisms of ALLHP are scarce. Aim of the studyTo verify the therapeutic effect of ALLHP on vitiligo and determine its effectiveness as a theoretical and experimental basis for the development of innovative drugs with independent intellectual property rights and the effective use of local resources. Materials and methodsThe experimental animal model of vitiligo was established by chemical decoloring. Rats were treated with gradient doses of ALLHP. The therapeutic effect was judged by gross observation. The contents of TYR, MAO, AchE and MDA in serum and skin tissue, the number of hair follicles containing melanin in skin tissue, the distribution of epidermal melanin, and the weight index of immune organs were detected, and the therapeutic effect of ALLHP on vitiligo was evaluated. In addition, certain monomer components in ALLHP were used to intervene in the zebrafish juvenile melanin suppression model, and the melanin-activating activities of some monomer components in ALLHP were screened by counting the melanin area ratio. ResultsALLHP increased the number of melanin-containing hair follicles and the epidermal melanin content in the skin of experimental vitiligo animals, repaired the skin cell morphology to a certain extent, increased the content of TYR in serum and skin, and reduced the content of MDA, AchE and MAO. Carvone, Luteolin, Psoralen and Psoraleae phenol and Bakuchiol could increase the melanin area of experimental melanin inhibition in zebrafish. ConclusionAccording to the results of this study, ALLHP can increase the number of melanin-containing hair follicles and the epidermal melanin content in the skin of vitiligo animals and restore skin cell morphology to a certain extent by reducing oxidative stress in epidermal tissue. A wide range of active ingredients may promote melanogenesis with ALLHP.

Antineoplastic Properties by Proapoptotic Mechanisms Induction of Inula viscosa and Its Sesquiterpene Lactones Tomentosin and Inuviscolide.

Cancer is a complex disease including approximately 200 different entities that can potentially affect all body tissues. Among the conventional treatments, radiotherapy and chemotherapy are most often applied to different types of cancers. Despite substantial advances in the development of innovative antineoplastic drugs, cancer remains one of the most significant causes of death, worldwide. The principal pitfall of successful cancer treatment is the intrinsic or acquired resistance to therapeutic agents. The development of more effective or synergistic therapeutic approaches to improve patient outcomes and minimize toxicity has become an urgent issue. Inula viscosa is widely distributed throughout Europe, Africa, and Asia. Used as a medicinal plant in different countries, I. viscosa has been characterized for its complex chemical composition in order to identify the bioactive compounds responsible for its biological activities, including anticancer effects. Sesquiterpene lactones (SLs) are natural, biologically active products that have attracted considerable attention due to their biological activities. SLs are alkylating agents that form covalent adducts with free cysteine residues within enzymes and key proteins favoring cancer cell cytotoxicity. They are effective inducers of apoptosis in several cancer cell types through different molecular mechanisms. This review focuses on recent advances in the cytotoxic effects of I. viscosa and SLs in the treatment of neoplastic diseases, with a special emphasis on their proapoptotic molecular mechanisms.

P fmdr 1 and kelch 13 genes distribution among children that are 5years and below in Akure, Nigeria.

Malaria parasite resistant to drugs has been a major barrier to effective treatment of malaria. Therefore, the study aimed to evaluate the distribution of Plasmodium falciparum resistant Kelch protein gene on chromosome 13 (Kelch 13) and multidrug resistant (Pfmdr1) mutant genes among children aged five years and below who attended Mother and Child Hospital, Akure, Nigeria. Thin and thick smears were prepared from the blood collected aseptically through venepuncture from five hundred (500) children. Structured questionnaires were used to obtain demographic data from the respondents. Two hundred malaria positive samples were randomly selected from the 500 samples for PCR analysis to detect Pfmdr1 and Kelch 13 mutant genes. The results showed that of the 500 respondents, 288 (57.6%) were males while 21 (42.4%) were females. Pfmdr1distribution include: mixed group (mutant/wild) 38.5%, mutant gene 35.5%, wild gene 20.5% and the resistant genes were absent in 5.5% of the infected children. The mixed group of Pfmdr1 gene was higher among infants (51.9%), children with birth order 4 (60.0%) and children that have blood group B (51.3%), however, there is no significant difference in the distribution of Pfmdr1 between gender (χ2 = 0.634, df = 1, p > 0.05). There was a point mutation in the codon position 557 where the amino acid Alanine was replaced by Serine in the PfK13. The presence of Pfmdr1 mutant genes and point mutation in the PfK13 gene of P. falciparum among children, calls for development of innovative drugs targeted on these resistant strains.