A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

Download Full-text

Synthesis of Drugs and Biorelevant N-heterocycles Employing Recent Advances in C-N Bond Formation

Current Organic Chemistry ◽

10.2174/1385272824999200909114144 ◽

2020 ◽

Vol 24 (20) ◽

pp. 2293-2340

Author(s):

Firdoos Ahmad Sofi ◽

Prasad V. Bharatam

Keyword(s):

Kinase Inhibitors ◽

Bond Formation ◽

Comprehensive Review ◽

Biologically Relevant ◽

Lead Compounds ◽

Heterocyclic Molecules ◽

The Past ◽

Anti Cancer ◽

Modern Methods ◽

Bond Formation Reactions

C-N bond formation is a particularly important step in the generation of many biologically relevant heterocyclic molecules. Several methods have been reported for this purpose over the past few decades. Well-known named reactions like Ullmann-Goldberg coupling, Buchwald-Hartwig coupling and Chan-Lam coupling are associated with the C-N bond formation reactions. Several reviews covering this topic have already been published. However, no comprehensive review covering the synthesis of drugs/ lead compounds using the C-N bond formation reactions was reported. In this review, we cover many modern methods of the C-N bond formation reactions, with special emphasis on metal-free and green chemistry methods. We also report specific strategies adopted for the synthesis of drugs, which involve the C-N bond formation reactions. Examples include anti-cancer, antidepressant, anti-inflammatory, anti-atherosclerotic, anti-histaminic, antibiotics, antibacterial, anti-rheumatic, antiepileptic and anti-diabetic agents. Many recently developed lead compounds generated using the C-N bond formation reactions are also covered in this review. Examples include MAP kinase inhibitors, TRKs inhibitors, Polo-like Kinase inhibitors and MPS1 inhibitors.

Download Full-text

Phytochemical and Pharmacological Review on Two Herbs of Baijiangcao: Patrinia scabiosaefolia Fisch. ex Trev. and Patrinia villosa (Thunb.) Juss

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x16666190617161124 ◽

2020 ◽

Vol 17 (5) ◽

pp. 496-517

Author(s):

Yangcheng Liu ◽

Wei Liu ◽

Jiaqi Wang ◽

Yang Liu ◽

Changlan Chen ◽

...

Keyword(s):

Chemical Constituents ◽

Volatile Components ◽

Research Papers ◽

Pharmacological Activities ◽

Comprehensive Review ◽

Scientific Databases ◽

The Past ◽

Current State ◽

Patrinia Scabiosaefolia ◽

Antiviral Activities

Patrinia scabiosaefolia Fisch. Trev. and Patrinia villosa (Thunb.) Juss, are two species of Patrinia recorded in the Chinese Pharmacopoeia with the same Chinese name “Baijiangcao” and similar therapeutic effect in traditional Chinese medicine. The present article is the first comprehensive review on the chemical composition and pharmacological activities of these herbs. In this review, data on chemical constituents and pharmacological profile of the two herbs are provided. This review discusses all the classes of the 223 compounds (phenylpropanoids, flavonoids, terpenes, saponins and volatile components, etc.) detected in the two herbs providing information on the current state of knowledge of the phytochemicals present in them. In the past three years, our research group has isolated and identified about more than 100 ingredients from the two herbs. Therefore, we published a systematic review of our research papers and studies on the two herbs were carried out using resources such as classic books about Chinese herbal medicine and scientific databases including Pubmed, Web of Science, SciFinder, CNKI. etc. The present review discusses the most thoroughly studied pharmacological activities (antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antitumor and antiviral activities) of the two herbs. This comprehensive review will be informative for scientists searching for new properties of these herbs and will be important and significant for the discovery of bioactive compounds from the two herbs and in complete utilization of Patrinia scabiosaefolia Fisch. ex Trev. and Patrinia villosa (Thunb.) Juss.

Download Full-text

Cucurbitacins as Anticancer Agents: A Patent Review

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892813666181119123035 ◽

2019 ◽

Vol 14 (2) ◽

pp. 133-143 ◽

Cited By ~ 3

Author(s):

Hidayat Hussain ◽

Ivan R. Green ◽

Muhammad Saleem ◽

Khanzadi F. Khattak ◽

Muhammad Irshad ◽

...

Keyword(s):

Anticancer Agents ◽

Wide Spectrum ◽

Biological Effects ◽

Therapeutic Effects ◽

Cytotoxic Effects ◽

Natural Sources ◽

Oh Groups ◽

Drug Candidates ◽

The Past ◽

Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

Download Full-text

Corrigendum to: Lamprothamnium in Australia (Characeae, Charophyceae)

Australian Systematic Botany ◽

10.1071/sb13026_co ◽

2013 ◽

Vol 26 (6) ◽

pp. 475

Author(s):

Michelle T. Casanova

Keyword(s):

New Species ◽

Species Level ◽

Type Material ◽

Review Of The Literature ◽

Comprehensive Review ◽

The Past

Charophytes in the genus Lamprothamnium exhibit a large amount of diversity, particularly in the examples from Australia, although little of that variation has been recognised at species level in the past. The Australian members of the genus are revised here on the basis of extensive new collections, examination of specimens in herbaria and comprehensive review of the literature and available type material. The existing species Lamprothamnium macropogon (A.Braun) Ophel, L. inflatum (Fil. & G.O.Allen ex Fil.) A.García & Karol and L. heraldii A.García & Casanova are retained, eight new species are described (L. australicum Casanova, L. beilbyae Casanova, L. capitatum Casanova, L. compactum Casanova, L. coorongense Casanova, L. diminutum Casanova, L. macroanthum Casanova and L. stipitatum Casanova) and two taxa variously treated at infraspecific rank in Lychnothamnus are transferred to Lamprothamnium at species rank (L. cockajemmyense Casanova, L. tasmanicum (A.Braun) Casanova). Neither L. papulosum (Wallr.) J.Groves nor L. succinctum (A.Braun) R.D.Wood are confirmed for Australia after examination of the type material of these species. Species are distinguished by the arrangement of the gametangia, morphology of the fertile whorls and characteristics of the oospores. Four of these species are dioecious and nine are monoecious, which supports published conjectures concerning the biogeography of charophyte species (Proctor (1980): J. Phycol. 16, 218–233, doi:10.1111/j.1529-8817.1980.tb03023.x).

Download Full-text

Men who have sex with men in China have relatively low numbers of sexual partners

Infectious Disease Reports ◽

10.4081/idr.2011.e10 ◽

2011 ◽

Vol 3 (1) ◽

pp. 10 ◽

Cited By ~ 4

Author(s):

Lei Zhang ◽

Eric Pui Fung Chow ◽

David P. Wilson

Keyword(s):

Median Number ◽

Sexual Partners ◽

Hiv Prevalence ◽

Comprehensive Review ◽

The Past ◽

Male Sexual Partners ◽

Sex With Men ◽

Over Time

HIV prevalence is increasing rapidly among men who have sex with men (MSM) in China and potentially associated with the number of male sexual partners that each man has on average. This study estimates the distribution of the number of male sexual partners among Chinese MSM through a comprehensive review of English and Chinese published literature. The overall median number of male sexual partners of Chinese MSM in the past 6 months China was estimated to be 1.5 (95% CI, 1.1-1.9) and 3.8 (95% CI 1.5-6.9) sexual partners in the past 6-month and 12-month periods respectively. An estimated 31% of sexual partners of MSM in China are regular partners, 54% are casual partners, and 16% are commercial partners. The reported numbers of sexual partners has not changed over time during the past decade. The numbers of male sexual partners reported by Chinese MSM is consistently lower than other settings and may not be sufficient to explain the recent rapid increase in HIV prevalence.

Download Full-text

Digestive involvement in COVID-19: what we have learned in the past 12 months

Medicine and Pharmacy Reports ◽

10.15386/mpr-2061 ◽

2021 ◽

Author(s):

Vladimir Posmag ◽

Liliana David ◽

Dan L. Dumitrascu

Keyword(s):

Observational Studies ◽

Digestive System ◽

Literature Search ◽

Gastrointestinal Symptoms ◽

Clinical Findings ◽

Treatment Schedule ◽

Gastrointestinal Involvement ◽

Comprehensive Review ◽

The Past ◽

The Relationship

Background and aim. The year 2020 will remain in the medical history as the year of COVID-19 pandemic. Although COVID-19 is considered mainly a respiratory disease, it is well known now that SARS-CoV-2 can affect major organs including the digestive system. This is a comprehensive review on gastrointestinal involvement in the SARS-CoV-2 infection, also the digestive damage due to COVID-19. Methods. A literature search was undertaken in main databases of medical publications following the search items digestive or gastrointestinal or gastric or enteral and SARS-CoV-2 or COVID-19. Data on gastrointestinal symptoms and alterations in this viral condition were collected and presented. Only observational studies were included. Results. In this review we discuss the recent information on the relationship between COVID-19 and the digestive system. The putative underlying pathogenic mechanisms of COVID-19 as well as the clinical findings in relation to gastrointestinal changes are presented. Conclusions. SARS-CoV-2 virus can affect any part of the digestive system. Patients with chronic diseases are at greatest risk of adverse out-comes. There is a considerable risk for drug-drug interactions in patients who require a large treatment schedule.

Download Full-text

Topoisomerases as anticancer targets

Biochemical Journal ◽

10.1042/bcj20160583 ◽

2018 ◽

Vol 475 (2) ◽

pp. 373-398 ◽

Cited By ~ 98

Author(s):

Justine L. Delgado ◽

Chao-Ming Hsieh ◽

Nei-Li Chan ◽

Hiroshi Hiasa

Keyword(s):

Anticancer Drugs ◽

Anticancer Agents ◽

Topoisomerase Ii ◽

Therapeutic Targets ◽

Strand Break ◽

Cancer Type ◽

Topoisomerase Inhibitors ◽

Topoisomerase Ii Poisons ◽

Topoisomerase Poisons ◽

Replication Fork Arrest

Many cancer type-specific anticancer agents have been developed and significant advances have been made toward precision medicine in cancer treatment. However, traditional or nonspecific anticancer drugs are still important for the treatment of many cancer patients whose cancers either do not respond to or have developed resistance to cancer-specific anticancer agents. DNA topoisomerases, especially type IIA topoisomerases, are proved therapeutic targets of anticancer and antibacterial drugs. Clinically successful topoisomerase-targeting anticancer drugs act through topoisomerase poisoning, which leads to replication fork arrest and double-strand break formation. Unfortunately, this unique mode of action is associated with the development of secondary cancers and cardiotoxicity. Structures of topoisomerase–drug–DNA ternary complexes have revealed the exact binding sites and mechanisms of topoisomerase poisons. Recent advances in the field have suggested a possibility of designing isoform-specific human topoisomerase II poisons, which may be developed as safer anticancer drugs. It may also be possible to design catalytic inhibitors of topoisomerases by targeting certain inactive conformations of these enzymes. Furthermore, identification of various new bacterial topoisomerase inhibitors and regulatory proteins may inspire the discovery of novel human topoisomerase inhibitors. Thus, topoisomerases remain as important therapeutic targets of anticancer agents.

Download Full-text

Recent Progress on Apoptotic Activity of Triazoles

Current Drug Targets ◽

10.2174/1389450122666210208181128 ◽

2021 ◽

Vol 22 ◽

Author(s):

Pelin Çıkla-Süzgün ◽

Ş. Güniz Küçükgüzel

Keyword(s):

Cancer Progression ◽

Anticancer Agents ◽

Heterocyclic Compounds ◽

Rational Design ◽

Vital Role ◽

Anticancer Activities ◽

The Past ◽

Small Molecule Drugs ◽

Apoptotic Activity ◽

New Generation

Abstract: Apoptosis, often called programmed cell death, is a self-directed cell destruction process. It differs from classical necrosis by activation of caspases. Apoptosis is directly related to cancer progression and plays a vital role in carcinogenesis. All cytotoxic drugs and radiation therapy programs initiates apoptosis in tumor cells. Today, studies show that heterocyclic compounds that contain triazole funtionality have anticancer activities. Triazoles are 5-membered rings, which contain two carbon and three nitrogen atoms Therefore, many researchers have synthesized these small active compounds as target structures and evaluated their apoptotic activities. The present review describs more recent medicinal aspects of triazoles as anticancer agents reported during the past few years. We hope that the bioactivity of triazole derivatives will be beneficial for the rational design of new generation of small molecule drugs.

Download Full-text

Maxillary Sinus Pneumocele Presenting as Aesthetic Deformity: A Case Report With Literature Review

Ear Nose & Throat Journal ◽

10.1177/0145561319850811 ◽

2019 ◽

Vol 99 (6) ◽

pp. 397-401

Author(s):

Hyun Sang Cho ◽

Seok Jung Hong ◽

Hyun Kyu Chae ◽

Kyung Soo Kim

Keyword(s):

Case Report ◽

Maxillary Sinus ◽

Surgical Approach ◽

Clinical Symptoms ◽

Interesting Case ◽

Operation Technique ◽

Comprehensive Review ◽

The Past ◽

Standard Operation ◽

Eye Symptoms

We report an interesting case of maxillary sinus pneumocele that presented with aesthetic deformity and completely treated with Caldwell-Luc approach and thoroughly review all of the past literature focusing on clinical symptoms and surgical approach. Based on our comprehensive review of maxillary sinus pneumocele, we found 2 important characteristics. First, maxillary sinus pneumocele may be asymptomatic but cause various symptoms owing to the displacement of neighboring structures, such as facial symptoms, eye symptoms, and nasal obstruction. Second, there is no standard operation technique for maxillary sinus pneumocele, but surgical approach should be individualized depending on patient’s symptoms and needs. Therefore, more case studies are needed to confirm this.

Download Full-text