Synthesis, screening and docking analysis of hispolon analogs as potential antitubercular agents

Balaji, Neduri V.; Babu, B. Hari; Subbaraju, Gottumukkala V.; Nagasree, Kurre Purna; Kumar, Muthyala Murali Krishna

doi:10.1016/j.bmcl.2016.11.047

Cited by 17 publications

(12 citation statements)

References 28 publications

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“…8 , 11 − 16 This has led researchers to synthesize new derivatives of HS and to explore them for various pharmacological activities. 20 − 22 In the present study, four compounds namely HS, HME, HP, and HMEP have been evaluated for chemical stability, toxicities, and antigenotoxic effects to identify a potential lead phytochemical for cancer chemotherapy and chemoprevention.…”

Section: Discussionmentioning

confidence: 99%

“…Considering the importance of HS as a pharmacological agent, several of its new derivatives have been synthesized and evaluated for antiproliferative and antitubercular effects. 20,21 On similar lines, recently our group reported the abilities of HS and its derivatives such as hispolon pyrazole (HP), hispolon monomethyl ether (HME), and hispolon monomethyl ether pyrazole (HMEP) to scavenge reactive oxygen species (ROS) and to exhibit antioxidant activity in cell-free systems. 22 The exposure of carcinogenic agents such as radiation, pollutants, and xenobiotics are known to increase the intracellular levels of ROS, leading to oxidative damages.…”

Section: Introductionmentioning

confidence: 91%

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Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase

Chethna¹,

Iyer²,

Gandhi

et al. 2018

ACS Omega

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Hispolon (HS), a bioactive polyphenol, and its derivatives such as hispolon monomethyl ether (HME), hispolon pyrazole (HP), and hispolon monomethyl ether pyrazole (HMEP) were evaluated for comparative toxicity and antigenotoxic effects. The stability of HS derivatives in biological matrices followed the order HS < HP ≈ HME < HMEP. The cytotoxicity analysis of HS derivatives indicated that HP and HMEP were less toxic than HS and HME, respectively, in both normal and tumor cell types. The mechanisms of toxicity of HS and HME involved inhibition of thioredoxin reductase (TrxR) and/or induction of reductive stress. From the enzyme kinetic and docking studies, it was established that HS and HME interacted with the NADPH-binding domain of TrxR through electrostatic and hydrophobic bonds, resulting in inhibition of the catalytic activity. Subsequently, treatment with HS, HP, and HMEP at a nontoxic concentration of 10 μM in Chinese Hamster Ovary (CHO) cells showed significant protection against radiation (4 Gy)-induced DNA damage as assessed by micronuclei and γ-H2AX assays. In conclusion, the above results suggested the importance of phenolic and diketo groups in controlling the stability and toxicity of HS derivatives. The pyrazole derivatives, HP and HMEP, may gain significance in the development of functional foods.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase

Chethna¹,

Iyer²,

Gandhi

et al. 2018

ACS Omega

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“…Thus, researchers linked the spirooxindole fragment and the benzofuran‐2‐one unit together via the cycloaddition reaction to determine the antitubercular activity of the derivatives. Compounds 10c and 10f exhibited prominent in vitro anti‐TB activities against M. tuberculosis H37Rv, with an MIC value as low as 1.56 μg/ml, which was four times better than the anti‐TB activity of the control drug pyrazinamide (Balaji, Hari, Subbaraju, Purna, & Murali, ).…”

Section: Five‐membered Ring Compoundsmentioning

confidence: 96%

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Wang

et al. 2020

Drug Development Research

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Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease.To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action. K E Y W O R D Santi-TB drug, antitubercular activities, five-membered ring, MDR-TB, tuberculosis

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“…The latter was up to 5 times more effective toward colon and prostate cancer cell lines [ 239 ]. Dehydrohispolon is a promising antitubercular agent showing lower MIC against M. tuberculosis with respect to hispolon [ 240 ]. Hispolon and hispolon methyl ether pyrazole derivatives ( Scheme 20 ) showed improved stability with respect to their precursors as well as antigenotoxic effects against radiation exposure [ 241 ].…”

Section: Diphenolsmentioning

confidence: 99%

Tailored Functionalization of Natural Phenols to Improve Biological Activity

et al. 2021

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Phenols are widespread in nature, being the major components of several plants and essential oils. Natural phenols’ anti-microbial, anti-bacterial, anti-oxidant, pharmacological and nutritional properties are, nowadays, well established. Hence, given their peculiar biological role, numerous studies are currently ongoing to overcome their limitations, as well as to enhance their activity. In this review, the functionalization of selected natural phenols is critically examined, mainly highlighting their improved bioactivity after the proper chemical transformations. In particular, functionalization of the most abundant naturally occurring monophenols, diphenols, lipidic phenols, phenolic acids, polyphenols and curcumin derivatives is explored.

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Synthesis, screening and docking analysis of hispolon analogs as potential antitubercular agents

Cited by 17 publications

References 28 publications

Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase

Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Tailored Functionalization of Natural Phenols to Improve Biological Activity

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