Improving the Physicochemical and Biopharmaceutical Properties of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicine through Cocrystal Engineering

Active pharmaceutical ingredients (APIs) extracted and isolated from traditional Chinese medicines (TCMs) are of interest for drug development due to their wide range of biological activities. However, the overwhelming majority of APIs in TCMs (T-APIs), including flavonoids, terpenoids, alkaloids and phenolic acids, are limited by their poor physicochemical and biopharmaceutical properties, such as solubility, dissolution performance, stability and tabletability for drug development. Cocrystallization of these T-APIs with coformers offers unique advantages to modulate physicochemical properties of these drugs without compromising the therapeutic benefits by non-covalent interactions. This review provides a comprehensive overview of current challenges, applications, and future directions of T-API cocrystals, including cocrystal designs, preparation methods, modifications and corresponding mechanisms of physicochemical and biopharmaceutical properties. Moreover, a variety of studies are presented to elucidate the relationship between the crystal structures of cocrystals and their resulting properties, along with the underlying mechanism for such changes. It is believed that a comprehensive understanding of cocrystal engineering could contribute to the development of more bioactive natural compounds into new drugs.

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Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures

Current Organic Synthesis ◽

10.2174/1570179416666190104141454 ◽

2019 ◽

Vol 16 (2) ◽

pp. 244-257 ◽

Cited By ~ 2

Author(s):

Marcus Vinicius Nora de Souza ◽

Cristiane França da Costa ◽

Victor Facchinetti ◽

Claudia Regina Brandão Gomes ◽

Paula Mázala Pacheco

Keyword(s):

Biological Activities ◽

Reaction Times ◽

Water Extract ◽

Fish Bone ◽

New Drugs ◽

Bone Powder ◽

Wide Range ◽

Recoverable Catalysts ◽

Egg Shell ◽

Work Up

Background: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. Methods: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. Results: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic β-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (β- CD); fish bone powder; nanoparticle-based catalyst, among others. Conclusion: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

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Identification of promising objects for the synthesis of thiosulphonate derivatives of benzoquinone and hydroquinone

Chemistry, Technology and Application of Substances ◽

10.23939/ctas2021.02.047 ◽

2021 ◽

Vol 4 (2) ◽

pp. 47-53

Author(s):

N. Y. Monka ◽

◽

N. E. Stadnytska ◽

I. R. Buchkevych ◽

K. O. Kaplia ◽

...

Keyword(s):

Biological Activity ◽

Biological Activities ◽

Experimental Studies ◽

New Drugs ◽

Reduced Form ◽

Free Form ◽

Wide Range ◽

On Line ◽

Living Organisms ◽

Derivatives Of

Benzoquinone and its reduced form hydroquinone belong to phenolic compounds and are found in living organisms in free form or in glycosides. They are active substances of some medicinal plants and have a pharmacological effect on the human body. Accordingly, their derivatives are important objects for chemical synthesis and development of new drugs. This article presents the findings of the structural design of substances with benzoquinone or hydroquinone fragment and sulfur-containing compound. By use of appropriate on-line programs a predictive screening of the biological activity and cytotoxicity of thiosulfonate derivatives of benzoquinone and hydroquinone has been conducted. It has been found that they have immense methodological potential to be synthesized by substances with a wide range of biological activities and a high value of probable activity, which substantiates the feasibility of conducting experimental studies on their biological activity, particularly anticancer.

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An Introduction to the Basic Concepts in QSAR-Aided Drug Design

Quantitative Structure-Activity Relationships in Drug Design, Predictive Toxicology, and Risk Assessment - Advances in Chemical and Materials Engineering ◽

10.4018/978-1-4666-8136-1.ch001 ◽

2015 ◽

pp. 1-47 ◽

Cited By ~ 4

Author(s):

Maryam Hamzeh-Mivehroud ◽

Babak Sokouti ◽

Siavoush Dastmalchi

Keyword(s):

Drug Design ◽

Drug Development ◽

Biological Activities ◽

Model Development ◽

Quantitative Structure Activity Relationship ◽

Molecular Structures ◽

New Drugs ◽

Qsar Modeling ◽

Qsar Studies ◽

Modern Drug

The need for the development of new drugs to combat existing and newly identified conditions is unavoidable. One of the important tools used in the advanced drug development pipeline is computer-aided drug design. Traditionally, to find a drug many ligands were synthesized and evaluated for their effectiveness using suitable bioassays and if all other drug-likeness features were met, the candidate(s) would possibly reach the market. Although this approach is still in use in advanced format, computational methods are an indispensable component of modern drug development projects. One of the methods used from very early days of rationalizing the drug design approaches is Quantitative Structure-Activity Relationship (QSAR). This chapter overviews QSAR modeling steps by introducing molecular descriptors, mathematical model development for relating biological activities to molecular structures, and model validation. At the end, several successful cases where QSAR studies were used extensively are presented.

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An Introduction to the Basic Concepts in QSAR-Aided Drug Design

Oncology ◽

10.4018/978-1-5225-0549-5.ch002 ◽

2017 ◽

pp. 20-66

Author(s):

Maryam Hamzeh-Mivehroud ◽

Babak Sokouti ◽

Siavoush Dastmalchi

Keyword(s):

Drug Design ◽

Drug Development ◽

Biological Activities ◽

Model Development ◽

Quantitative Structure Activity Relationship ◽

Molecular Structures ◽

New Drugs ◽

Qsar Modeling ◽

Qsar Studies ◽

Modern Drug

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Funding of clinical trials in Brazil for the development of new drugs: who are the sponsors?

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20151236 ◽

2015 ◽

Vol 2 (4) ◽

pp. 75 ◽

Cited By ~ 1

Author(s):

Ricardo Eccard da Silva ◽

Angélica Amorim Amato ◽

Maria Rita Carvalho Garbi Novaes

Keyword(s):

Clinical Trials ◽

Pharmaceutical Industry ◽

The Other ◽

New Drugs ◽

Essential Medicines ◽

Neglected Diseases ◽

Active Pharmaceutical Ingredients ◽

Pharmaceutical Ingredients ◽

Funding Sources ◽

Other Hand

Background: A low rate of investment in science it is directly impacts the technological independence and capacity in health care costs. Knowledge of funding sources is critical to understand the problem and formulates hypotheses for future studies.Methods: Two databases were used: the System for Control of Clinical Research (SCCR) from the Brazilian Health Surveillance Agency (Anvisa), and the International Clinical Trials Registry Platform (ICTRP). Results: From 2009 to 2012, 77% of the clinical trials approved by Anvisa were sponsored by transnational pharmaceutical industry. On the other hand, the national pharmaceutical industry sponsored 8% of the trials over the same period. The most frequent sponsor of clinical trials involving drugs registered in the ICTRP from 2011 to 2012 was the transnational pharmaceutical industry (43%). Among the trials with national sponsors, are those involving neglected diseases such as chronic hepatitis C (ICD X B18.2), cutaneous leishmaniasis (ICD X B55.1) and yellow fever (ICD X A95), which were all sponsored by national governmental foundations. None of the active pharmaceutical ingredients studied by the transnational pharmaceutical industry or the transnational biopharmaceutical company were in the national list of essential medicines. On the other hand, 83% and 66.6% of the active pharmaceutical ingredients studied by national private universities and the international governmental agency, respectively, are in the national list of essential medicines. Conclusions: The national pharmaceutical industry and government still invests little in Research and Development (R&D) activities, when compared with transnational industries. This affects directly its technological and innovation ability.

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Polyoxometalates in Biomedicine: Update and Overview

Current Medicinal Chemistry ◽

10.2174/0929867326666190827153532 ◽

2020 ◽

Vol 27 (3) ◽

pp. 362-379 ◽

Cited By ~ 7

Author(s):

Mirjana B. Čolović ◽

Milan Lacković ◽

Jovana Lalatović ◽

Ali S. Mougharbel ◽

Ulrich Kortz ◽

...

Keyword(s):

Biological Activities ◽

Transition Metal Ions ◽

Fine Tuning ◽

Comprehensive Overview ◽

Early Transition Metal ◽

Biological Targets ◽

Wide Range ◽

Treatment Of Diabetes

Background: Polyoxometalates (POMs) are negatively charged metal-oxo clusters of early transition metal ions in high oxidation states (e.g., WVI, MoVI, VV). POMs are of interest in the fields of catalysis, electronics, magnetic materials and nanotechnology. Moreover, POMs were shown to exhibit biological activities in vitro and in vivo, such as antitumor, antimicrobial, and antidiabetic. Methods: The literature search for this peer-reviewed article was performed using PubMed and Scopus databases with the help of appropriate keywords. Results: This review gives a comprehensive overview of recent studies regarding biological activities of polyoxometalates, and their biomedical applications as promising anti-viral, anti-bacterial, anti-tumor, and anti-diabetic agents. Additionally, their putative mechanisms of action and molecular targets are particularly considered. Conclusion: Although a wide range of biological activities of Polyoxometalates (POMs) has been reported, they are to the best of our knowledge not close to a clinical trial or a final application in the treatment of diabetes or infectious and malignant diseases. Accordingly, further studies should be directed towards determining the mechanism of POM biological actions, which would enable fine-tuning at the molecular level, and consequently efficient action towards biological targets and as low toxicity as possible. Furthermore, biomedical studies should be performed on solutionstable POMs employing physiological conditions and concentrations.

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Fastidious Anatomization of Biota Procured Compounds on Cancer Drug Discovery

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666191128145015 ◽

2020 ◽

Vol 21 (5) ◽

pp. 354-363

Author(s):

Anand Thirupathi ◽

Chandra M. Shanmugavadivelu ◽

Sampathkumar Natarajan

Keyword(s):

Natural Products ◽

Side Effects ◽

Cancer Therapy ◽

Biological Activities ◽

Drug Approval ◽

Current Treatment ◽

New Drugs ◽

Cancer Drug ◽

Synthetic Drugs ◽

Wide Range

Background: Natural products are the rootstock for identifying new drugs since ancient times. In comparison with synthetic drugs, they have abounding beneficial effects in bestowing protection against many diseases, including cancer. Cancer has been observed as a major threat in recent decades, and its prevalence is expected to increase over the next decades. Also, current treatment methods in cancer therapy such as radiation therapy and chemotherapy cause severe adverse side effects among the cancer population. Therefore, it is exigent to find a remedy without any side effects. Methods: In recent years, research has focused on obtaining naturally derived products to encounter this complication. The current pace of investigations, such as gene identification and advancement in combinatorial chemistry, leads to the aberrant access to a wide range of new synthetic drugs. In fact, natural products act as templates in structure predictions and synthesis of new compounds with enhanced biological activities. Results: Recent developments in genomics have established the importance of polymorphism, which implies that patients require different drugs for their treatment. This demands the discovery of a large number of drugs, but limited sources restrict the pharmaceutical industry to overcome these major obstacles. The use of natural products and their semisynthetic and synthetic analogues could alleviate these problems. However, the lack of standardization in terms of developing methods for evaluating the chemical composition, efficacy, isolation and international approval is still a major limitation in this field. In the past few years, several drug-approval authorities, including the FDA and WHO have allowed using these naturally derived compounds in humans. Conclusion: In this review, we described the use of some natural products from plant and marine sources in cancer treatment and shed some light on semi-synthetic and synthetic compounds derived from natural sources used in cancer therapy.

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Current Pharmaceutical Aspects of Synthetic Quinoline Derivatives

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520999201214234735 ◽

2020 ◽

Vol 20 ◽

Author(s):

Rukhsana Tabassum ◽

Muhammad Ashfaq ◽

Hiroyuki Oku

Keyword(s):

Fungal Infections ◽

Biological Activities ◽

Chemical Properties ◽

New Drugs ◽

Quinoline Derivatives ◽

Wide Range ◽

Anti Cancer ◽

Anti Fungal ◽

Physical And Chemical ◽

And Chemical Properties

Abstract:: Quinoline derivatives are considered as broad spectrum pharmacological compounds that exhibit wide range of biological activities. Integration of quinoline moiety can improve its physical and chemical properties and also pharmacological behavior. Due to its wide range of pharmaceutical applications it is very popular compound to design new drugs for treatment of multiple diseases like cancer, dengue fever, malaria, tuberculosis, fungal infections, AIDS, Alzheimer’s disease and diabetes . In this review our major focus is to pay attention on biological activities of quinoline compounds in treatment of these diseases such as, anti-viral, anti-cancer, anti-malarial, anti-bacterial, anti-fungal, anti-tubercular and anti-diabetic.

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Benzoylthioureas: Design, Synthesis and Antimycobacterial Evaluation

Medicinal Chemistry ◽

10.2174/1573406415666181208110753 ◽

2020 ◽

Vol 16 (1) ◽

pp. 93-103

Author(s):

Tiago O. Brito ◽

Lethícia O. Abreu ◽

Karen M. Gomes ◽

Maria C.S. Lourenço ◽

Patricia M.L. Pereira ◽

...

Keyword(s):

Benzene Ring ◽

Biological Activities ◽

Antitubercular Activity ◽

Antimycobacterial Activity ◽

New Drugs ◽

Design Synthesis ◽

Thiourea Derivatives ◽

Structural Modifications ◽

General Series ◽

Wide Range

Background: New drugs and strategies to treat tuberculosis (TB) are urgently needed. In this context, thiourea derivatives have a wide range of biological activities, including anti-TB. This fact can be illustrated with the structure of isoxyl, an old anti-TB drug, which has a thiourea as a pharmacophore group. Objective: The aim of this study is to describe the synthesis and the antimycobacterial activity of fifty-nine benzoylthioureas derivatives. Methods: Benzoylthiourea derivatives have been synthesized and evaluated for their activity against Mycobacterium tuberculosis using the MABA assay. After that, a structure-activity relationship study of this series of compounds has been performed. Results and Discussion: Nineteen compounds exhibited antimycobacterial activity between 423.1 and 9.6 μM. In general, we observed that the presence of bromine, chlorine and t-Bu group at the para-position in benzene ring plays an important role in the antitubercular activity of Series A. These substituents were fixed at this position in benzene ring and other groups such as Cl, Br, NO2 and OMe were introduced in the benzoyl ring, leading to the derivatives of Series B. In general, Series B was less cytotoxic than Series A, which indicates that the presence of a substituent at benzoyl ring contributes to an improvement in both antimycobacterial activity and toxicity profiles. Conclusion: Compound 4c could be considered a good prototype to be submitted to further structural modifications in the search for new anti-TB drugs, since it is 1.8 times more active than the first line anti-TB drug ethambutol and 0.65 times less active than isoxyl.

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Ethnopharmacological uses, biological activities, chemistry and toxicological aspects of Ocimum americanum var. americanum (Lamiaceae)

The Journal of Phytopharmacology ◽

10.31254/phyto.2021.10111 ◽

2021 ◽

Vol 10 (1) ◽

pp. 56-60

Author(s):

Hashim Mohamed Ali ◽

◽

Joseph Mwanzia Nguta ◽

Isaac Ole Mapenay ◽

Fredrick Mutie Musila ◽

...

Keyword(s):

Literature Search ◽

Biological Activities ◽

Eastern Africa ◽

Comprehensive Overview ◽

Toxicological Effects ◽

Accessible Information ◽

Wide Range ◽

Toxicological Data ◽

Phytochemical Constituents ◽

Ocimum Americanum

The rationale for the use of Ocimum americanum var. americanum in herbal medicine is largely based on the longstanding experience of traditional medicine practitioners. The genus Ocimum is extensively used in Eastern Africa in folkloric practice against a wide range of illnesses. The present paper intends to bring a comprehensive overview of O. americanum var. americanum in regard to its biological activities, ethnopharmacological uses, phytochemical and toxicological effects. The literature search was conducted using Google, Google Scholar, Chemical abstracts, Sciverse; JSTOR, Medline, PubMed, Science Direct, Scopus and Springer Link. O. americanum var. americanum extracts have been shown to have antimicrobial, antioxidant, antiproliferative, insecticidal, and repellent activities. Literature on the activity of O. americanum var. americanum extracts against metabolic syndromes such as diabetes, hyperlipidaemias and hypertension is scanty. Toxicological data is also limited; however, the accessible information indicates non-toxicity of O. americanum var. americanum extracts. Substantial variations in phytochemical constituents of this particular species are observed, which may be attributed to edaphic differences as well as ecoclimatic regions.

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