Development of 'S', 'N’ Heterocycles as Antimycobacterials Targeting Fatty Acid Biosynthesis

2019 ◽  
Vol 15 ◽  
Author(s):  
L. K. Dahiwade ◽  
S. R. Rochlani ◽  
P. B. Choudhari ◽  
R. P. Dhavale ◽  
H. N. Moreira
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Antimycobacterial Activity ◽  
Drug Candidate ◽  
Causative Organism ◽  
Present Communication ◽  
Acid Biosynthesis ◽  
Rational Development ◽  
After Cancer ◽  
Drug Resistant Strains

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most deadly disease after cancer in a current decade. The development of multidrug and broadly drug- resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Objectives: Reported here are the development of 'S', 'N’ heterocycles as antimycobacterials targeting fatty acid biosynthesis. Material and Methods: In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modelling and virtual analysis. Results: The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. Conclusion: In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidate having less side effects.

Inhibition of early steps of de novo fatty-acid biosynthesis by different xenobiotica

1991 ◽  
Vol 81 (2) ◽  
pp. 251-255
Author(s):  
Manfred Focke ◽  
Andrea Feld ◽  
Hartmut K. Lichtenthaler
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acid Biosynthesis

scholarly journals Genome-Wide Mapping of Histone H3 Lysine 4 Trimethylation (H3K4me3) and Its Involvement in Fatty Acid Biosynthesis in Sunflower Developing Seeds

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 706
Author(s):  
Antonio J. Moreno-Pérez ◽  
Raquel Martins-Noguerol ◽  
Cristina DeAndrés-Gil ◽  
Mónica Venegas-Calerón ◽  
Rosario Sánchez ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Fatty Acid Biosynthesis ◽  
Acid Synthesis ◽  
Sunflower Seeds ◽  
Acid Biosynthesis ◽  
Functional Regions ◽  
Genome Wide

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.

scholarly journals Serratia symbiotica Enhances Fatty Acid Metabolism of Pea Aphid to Promote Host Development

2021 ◽  
Vol 22 (11) ◽  
pp. 5951
Author(s):  
Xiaofei Zhou ◽  
Xiaoyu Ling ◽  
Huijuan Guo ◽  
Keyan Zhu-Salzman ◽  
Feng Ge ◽  
...  
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Myristic Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis ◽  
Pea Aphids ◽  
Serratia Symbiotica ◽  
Aphid Host ◽  
Host Development

Bacterial symbionts associated with insects are often involved in host development and ecological adaptation. Serratia symbiotica, a common facultative endosymbiont harbored in pea aphids, improves host fitness and heat tolerance, but studies concerning the nutritional metabolism and impact on the aphid host associated with carrying Serratia are limited. In the current study, we showed that Serratia-infected aphids had a shorter nymphal developmental time and higher body weight than Serratia-free aphids when fed on detached leaves. Genes connecting to fatty acid biosynthesis and elongation were up-regulated in Serratia-infected aphids. Specifically, elevated expression of fatty acid synthase 1 (FASN1) and diacylglycerol-o-acyltransferase 2 (DGAT2) could result in accumulation of myristic acid, palmitic acid, linoleic acid, and arachidic acid in fat bodies. Impairing fatty acid synthesis in Serratia-infected pea aphids either by a pharmacological inhibitor or through silencing FASN1 and DGAT2 expression prolonged the nymphal growth period and decreased the aphid body weight. Conversely, supplementation of myristic acid (C14:0) to these aphids restored their normal development and weight gain. Our results indicated that Serratia promoted development and growth of its aphid host through enhancing fatty acid biosynthesis. Our discovery has shed more light on nutritional effects underlying the symbiosis between aphids and facultative endosymbionts.

scholarly journals The Regulation of Fatty Acid Biosynthesis in Human Skin Fibroblasts

1973 ◽  
Vol 248 (4) ◽  
pp. 1268-1276 ◽  
Author(s):  
Richard A. Jacobs ◽  
William S. Sly ◽  
Philip W. Majerus
Keyword(s):  
Fatty Acid ◽  
Human Skin ◽  
Fatty Acid Biosynthesis ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Acid Biosynthesis

scholarly journals The Condensation Reaction of Fatty Acid Biosynthesis

1963 ◽  
Vol 238 (4) ◽  
pp. 1255-1261 ◽  
Author(s):  
Peter Goldman ◽  
A.W. Alberts ◽  
P. Roy Vagelos
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Condensation Reaction ◽  
Acid Biosynthesis

scholarly journals Cloning and functional analysis of the FAD2 gene family from desert shrub Artemisia sphaerocephala

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiumei Miao ◽  
Lijing Zhang ◽  
Xiaowei Hu ◽  
Shuzhen Nan ◽  
Xiaolong Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Linoleic Acid ◽  
Gene Family ◽  
Fatty Acid Biosynthesis ◽  
Family Members ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Acid Biosynthesis ◽  
Desert Shrub ◽  
Artemisia Sphaerocephala

Abstract Background Linoleic acid is an important polyunsaturated fatty acid, required for all eukaryotes. Microsomal delta-12 (Δ12) oleate desaturase (FAD2) is a key enzyme for linoleic acid biosynthesis. Desert shrub Artemisia sphaerocephala is rich in linoleic acid, it has a large FAD2 gene family with twenty-six members. The aim of this work is to unveil the difference and potentially functionality of AsFAD2 family members. Results Full-length cDNAs of twenty-one AsFAD2 genes were obtained from A. sphaerocephala. The putative polypeptides encoded by AsFAD2 family genes showed a high level of sequence similarity and were relatively conserved during evolution. The motif composition was also relatively conservative. Quantitative real-time PCR analysis revealed that the AsFAD2–1 gene was strongly expressed in developing seeds, which may be closely associated with the high accumulating ability of linoleic acid in A. sphaerocephala seeds. Although different AsFAD2 family members showed diverse response to salt stress, the overall mRNA levels of the AsFAD2 family genes was stable. Transient expression of AsFAD2 genes in the Nicotiana benthamiana leaves revealed that the encoded proteins were all located in the endoplasmic reticulum. Heterologous expression in Saccharomyces cerevisiae suggested that only three AsFAD2 enzymes, AsFAD2–1, − 10, and − 23, were Δ12 oleate desaturases, which could convert oleic acid to linoleic acid, whereas AsFAD2–1 and AsFAD2–10 could also produce palmitolinoleic acid. Conclusions This research reported the cloning, expression studies, subcellular localization and functional identification of the large AsFAD2 gene family. These results should be helpful in understanding fatty acid biosynthesis in A. sphaerocephala, and has the potential to be applied in the study of plant fatty acids traits.

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