Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors

Rao, A. V. Subba; Vardhan, M.V.P.S. Vishnu; Reddy, N. V. Subba; Reddy, T. Srinivasa; Shaik, Siddiq Pasha; Bagul, Chandrakant; Kamal, Ähmed

doi:10.1016/j.bioorg.2016.09.002

Cited by 38 publications

(9 citation statements)

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“…Topoisomerase-mediated DNA relaxation assays. Some oxadiazole derivatives have also been reported to have inhibitory activity on topoisomerases (20,21), so the same three compounds, endowed with the highest antiproliferative activity (1,2 and 4), were tested against topoisomerase II (Table II).…”

Section: Resultsmentioning

confidence: 99%

Unravelling the Antiproliferative Activity of 1,2,5-oxadiazole Derivatives

et al. 2019

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Background: Our efforts, focused on the discovery of novel antiproliferative agents, led to the identification of an interesting oxadiazole derivative, MD77. Aim: To complete the studies concerning the antiproliferative profile of MD77 , we developed several new derivatives. Materials and Methods: The substitution pattern around the phenyl rings of this compound was analysed through the synthesis of positional isomers and of analogues bearing different substituents at the para positions (2-12). Results: The results of the antiproliferative activity of these derivatives versus HCT-116 and HeLa cancer cell lines shed light on the effects of the presence, nature and position of such substituents. Notably, derivative 4, a regioisomer of 1 in which the substituents at the para positions of the phenyl rings were inverted, showed the best antiproliferative profile, exhibiting a significant activity also against MCF7 and MDA-MB 468 cancer cell lines. Conclusion: Preliminary results showed the ability of compound 4 to counteract human recombinant topoisomerase II α relaxation activity.

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Section: Resultsmentioning

confidence: 99%

Unravelling the Antiproliferative Activity of 1,2,5-oxadiazole Derivatives

et al. 2019

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“…Another important enzyme involved in DNA biology is DNA Topoisomerase II (topo II), which controls DNA structure by catalyzing DNA cleavage and phosphodiester bonds degradation. Recently, topo II inhibitors became clinically useful as chemotherapeutical agents, and in this slice Rao et al have developed imidazopyridinyl-1,3,4-oxadiazole conjugates, among which 38 ( Figure 7 ) was able to affect the catalytic activity of this specific enzyme [ 58 ]. In particular, it exhibited a great growth cell inhibition in a panel of sixty cancer cell lines (mean growth of 33.54%) among which the most sensitive cell line was a non-small cell lung cancer (HOP-62).…”

Section: Enzyme Interactionsmentioning

confidence: 99%

“…Subsequently, the authors verified the ability of 38 in causing cell cycle arrest at sub G1 phase till 41.70%, as well as reduction of cell population in G1 phase. Once its induced apoptotic activity was identified, increasing in intracellular ROS production was also verified, suggesting that cytotoxicity and apoptosis caused by 38 probably resulted from the mitochondrial pathway [ 58 ].…”

Section: Enzyme Interactionsmentioning

confidence: 99%

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

Benassi

Doria

Pirota

2020

IJMS

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Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles—five-membered aromatic rings—emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazole-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins, and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.

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“…The series were further improved, however the synthesis schemes remain quite lengthy and this could be a deterrent factor for the development of the scaffold in the future. Compounds with the same bis‐heterocycles were also described as topoisomerase IIα inhibitors (Scheme ) . It should be noted that in both cases the two heterocycles are constructed separately in a multi‐step synthesis.…”

Section: Introductionmentioning

confidence: 99%

Sequential Multicomponent Synthesis of 2‐(Imidazo[1,5‐α]pyridin‐1‐yl)‐1,3,4‐Oxadiazoles

et al. 2019

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A 21 membered library of 2‐(imidazo[1,5‐α]pyridine‐1‐yl)‐1,3,4‐oxadiazoles is synthesized in an unprecedented short sequence starting from an Ugi tetrazole reaction with a cleavable isocyanide component. The intermediate tetrazole is subjected to an acetic anhydride‐mediated cyclization, followed by a Huisgen‐type rearrangement with acyl chlorides to afford the imidazopyridine‐oxadiazole bis‐heterocycles. The scope and limitations of the methodology were investigated with substitutions on both the oxadiazole and the imidazopyridine rings. The introduced enabling technology for imidazopyridine oxadiazole synthesis combines a short reaction sequence with high scaffold diversity, based on commercially available starting materials and high functional groups tolerance.

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Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors

Cited by 38 publications

References 50 publications

Unravelling the Antiproliferative Activity of 1,2,5-oxadiazole Derivatives

Unravelling the Antiproliferative Activity of 1,2,5-oxadiazole Derivatives

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

Sequential Multicomponent Synthesis of 2‐(Imidazo[1,5‐α]pyridin‐1‐yl)‐1,3,4‐Oxadiazoles

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