Insights from the molecular docking of withanolide derivatives to the target protein PknG from Mycobacterium tuberculosis

Santhi, Natchimuthu; Sekar, Aishwarya

doi:10.6026/97320630007001

Cited by 25 publications

(15 citation statements)

References 11 publications

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“…Another molecular docking studies with 40 withanolide derivates, an ayurvedic herb, suggested four compounds withanolide E, D, F and withaferin inhibited PknG. These compounds inhibited PknG by interacting with active side residues, like AX20017 . However, the potency of withanolide derivates to kill the intracellular bacteria has not been yet determined.…”

Section: Inhibitorsmentioning

confidence: 99%

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

2018

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The emergence of increasingly drug-resistant Mycobacterium tuberculosis strains has become a crucial public health concern. In order to effectively treat tuberculosis, it is imperative to find newer drug targets, which are important for the in vivo bacterial survival and persistence. Phosphorylation based signaling cascades modulated by eukaryotic-like serine/threonine protein kinases and phosphatase in M. tuberculosis, transduce extracellular stimuli to a cellular response ensuing pathogen's growth, persistence and pathogenesis. Of the 11 STPKs that M. tuberculosis genome encodes, three kinases, namely PknA, PknB and PknG and the sole serine/threonine phosphatase PstP are crucial for the intracellular survival of the bacteria. PknA and PknB regulates cell growth, cell wall synthesis and morphological changes during bacterial cell division; while PknG modulates metabolic changes in response to stress and aids in bacterial survival during latency like conditions. PstP functions to dephosphorylate STPKs and their substrates and hence is important at nearly all stages of infection. Here, we review the current knowledge on PstP, PknA, PknB and PknG based on the genetic, biochemical, and functional studies in M. tuberculosis physiopathology. We further explore the potential of these molecules as targets for therapeutic intervention and discuss the advancement made in the development of inhibitors against these targets. © 2018 IUBMB Life, 70(9):889-904, 2018.

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Section: Inhibitorsmentioning

confidence: 99%

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

2018

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“…Its therapeutic effects have been mainly attributed to steroidal lactones, collectively known as withanolides, which have a wide range of biological actions 29. It has been used for centuries for a variety of conditions and this case report is the first to describe a benefit in a patient with NCAH.…”

Section: Discussionmentioning

confidence: 88%

Ashwagandharoot in the treatment of non-classical adrenal hyperplasia

Kalani

Bahtiyar

Sacerdote³

2012

BMJ Case Reports

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SummaryCongenital adrenal hyperplasia (CAH) is a well-characterised family of disorders of the adrenal cortices, resulting in varying degrees of cortisol, aldosterone and androgen deficiency or androgen excess, depending on the enzyme(s) affected and the degree of quantitative or functional enzyme deficit. Withania somnifera (WS), commonly known as Ashwagandha, is a medicinal plant that has been employed for centuries in ayurvedic medicine. Preclinical studies have shown that WS increases circulating cortisol levels and improves insulin sensitivity. We report the case of a 57-year-old woman with non-classical adrenal hyperplasia due to both 3-β-ol dehydrogenase deficiency and aldosterone synthase deficiency who was self-treated with WS for 6 months. After 6 months of treatment her serum 18-OH-hydroxycorticoserone, 17-OH-pregnenolone, corticosterone and 11-deoxycortisol decreased by 31%, 66%, 69% and 55%, respectively. The biochemical improvement was accompanied by a noticeable reduction in scalp hair loss. BACKGROUND

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“…It is also shown to be a moderate to active against Microsporum gypseum, Candida albicans and Cryptococcus neoformans (Mwitari et al, 2013). Withanolide D, E and F showed potent activity against PknG target in Mycobacterium tuberculosis (Santhi and Aishwarya, 2011). It has also been shown in different studies that W. somnifera have the best antimicrobial (1.5625 mg/ml), immunopotentiation (2 times IL-7 mRNA expression) and safety level (IC50 200 mg/ml).…”

Section: Antimicrobial Activitymentioning

confidence: 93%

Chemistry and pharmacology of withania somnifera: An update

Kumar¹,

Dey²,

Hadimani³

et al. 2015

TANG [HUMANITAS MEDICINE]

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Withania somnifera (Ashwagandha) is an important Rasayana herb and widely considered as Indian ginseng in Ayurveda. In traditional system of Indian medicine, it is used as tonic to rejuvenate the body and increase longevity. In Ayurvedic preparations, various parts of the plant have been used to treat variety of ailments that affect the human health. However, dried roots of the plant are widely used for the treatment of nervous and sexual disorders. The major active chemical constituents of this plant are withanolides, which is responsible for its wide range of biological activities. Since the beginning of the 20 th century, a significant amount of research has been done and efforts are ongoing to further explore other bioactive constituents, and many pharmacological studies have been carried out to describe their disease preventing mechanisms. In this chapter, we have reviewed the chemistry and pharmacological basis of W. somnifera in various human ailments.

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Insights from the molecular docking of withanolide derivatives to the target protein PknG from Mycobacterium tuberculosis

Cited by 25 publications

References 11 publications

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

Ashwagandharoot in the treatment of non-classical adrenal hyperplasia

Chemistry and pharmacology of withania somnifera: An update

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