Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review

Fang, Wan‐Yin; Lekkala, Ravindar; Rakesh, K.P.; Manukumar, H.M.; Shantharam, C.S.; Alharbi, Njud S.; Qin, Hua‐Li

doi:10.1016/j.ejmech.2019.03.063

Cited by 156 publications

(89 citation statements)

References 111 publications

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“…The base pairs of DNA and RNA (guanine, cytosine, adenine, and thymine) are also made up of N-heterocyclic compounds, namely purines, pyrimidines, etc. These nitrogen-containing heterocyclic molecules with distinct characteristics and applications have gained prominence in the rapidly expanding fields of organic and medicinal chemistry and the pharmaceutical industry [11][12][13]. Furthermore, the electron-rich nitrogen heterocycle is not only able to readily accept or donate a proton, but it can also easily establish diverse weak interactions.…”

Section: Introductionmentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

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Section: Introductionmentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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“…Further, their metabolism in the body does not result in toxic metabolites so, this selection of co-formers is not only safe for in-vivo administration but can also be helpful in the improvement of 5-FU pharmacological properties (Langley and Rothwell, 2012, Li, 2017, Rakesh, 2017). The major elements in all the selected co-formers like F, S, O, N and H are among the top ten elements in approved drugs (Fang, 2019). Co-crystals of 5-FU are prepared by following the solid-state grinding method and solution method, with the use of methanol as a solvent.…”

Section: Introductionmentioning

confidence: 99%

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Jubeen

Liaqat

Sultan

et al. 2019

Saudi Pharmaceutical Journal

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This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e., solid-state grinding protocol, in which API and co-formers were mixed through vigorous grinding while in the other method separate solutions of both the components were made and mixed together. The adopted approaches offer easy fabrication protocols, no temperature maintenance requirements, no need of expensive solvents, hardly available apparatus, isolation and purification of the desired products. In addition, there is no byproducts formation, In fact, a phenomenon embracing the requirements of green synthesis. Through FTIR analysis; for API the N—H absorption frequency was recorded at 3409.02 cm−1 and that of —CO was observed at 1647.77 cm−1. These characteristics peaks of 5-FU were significantly shifted and recorded at 3499.40 cm−1 and 1649.62 cm−1 for 5-FU-Ac (3B) and 3496.39 cm−1 and 1659.30 cm−1 for 5-FU-As (4B) co-crystals for N—H and —CO groups respectively. The structural differences between API and co-crystals were further confirmed through PXRD analysis. The characteristic peak of 5-FU at 2θ = 28.79918o was significantly shifted in the graphs of co-crystals not only in position but also with respect to intensity and FWHM values. In addition, new peaks were also recorded in all the spectra of co-formers confirming the structural differences between API and co-formers. In addition, percent growth inhibition was also observed by all the co-crystals through MTT assay against HCT 116 colorectal cell lines in vitro. At four different concentrations; 25, 50, 100 and 200 µg/mL, slightly different trends of the effectiveness of API and co-crystals were observed. However; among all the co-crystal forms, 5-FU-thiourea co-crystals obtained through solution method (2B) proved to be the most effective growth inhibitor at all the four above mentioned concentrations.

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“…The presence of chlorine as a substituent in many drugs appears to be responsible for bioactivity. Fang et al [ 35 ] reported that a total of 163 compounds out of the 233 drugs approved for clinical uses contain chlorine in their structures. Among the 163 compounds, nearly 73% of them possess one chlorine atom whilst 23%, 2.6%, 1.4%, and 2.5% of such compounds were found to have two, three, four, and six chlorine atoms in their molecular structures, respectively [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

“…Fang et al [ 35 ] reported that a total of 163 compounds out of the 233 drugs approved for clinical uses contain chlorine in their structures. Among the 163 compounds, nearly 73% of them possess one chlorine atom whilst 23%, 2.6%, 1.4%, and 2.5% of such compounds were found to have two, three, four, and six chlorine atoms in their molecular structures, respectively [ 35 ]. The current market for chlorine containing drugs is worth approximately USD 168.5 billion, of which anti-infectives and cytostatics account for USD 9.5 and 12.7 billion, respectively [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

et al. 2020

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Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC50 value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities.

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Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review

Cited by 156 publications

References 111 publications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

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