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The imperative for the expeditious development of novel antibiotics stems from the escalating resistance trends witnessed against conventional antibiotic agents.The present study delineates the synthesis, characterization, and antibacterial efficacy of β,β-disubstituted-β-amino acid derivatives, specifically those capped with lauric acid at the N-terminus through amide and urea bonds, LA-β^3,3-Pip-PEA, 1; LA-β^3,3-Pip(G)-PEA, 2; LA^U-β^3,3-Pip-PEA, 3; and LA^U-β^3,3-Pip(G)-PEA, 4.Against E. coli, S. aureus, and E. faecalis LA^U-β^3,3-Pip-PEA, 3 exhibited robust antibacterial activity having a low min. inhibitory concentration (MIC) of 0.5 μg/mL.It also showed a remarkable MIC of 8 μg/mL and 16 μg/mL against MRSA and MDR E. coli resp. outperforming amoxicillin, cefpodoxime, and 10 other standard antibiotics.It also synergized with antibiotics like Ciprofloxacin, Streptomycin, and Ampicillin.Mechanistic insights revealed membrane disruption in E. coli and S. aureus upon treatment with compound 3.Compound 3 maintained complete cell viability across observed cell lines; AML12, RAW 264.7, and HEK-293 at concentrations of 1 μg/mL and 10 μg/mL.Demonstrating notable stability, compound 3 resisted trypsin degradation and maintained antibacterial efficacy across diverse temperatures and pH conditions.Concentration-dependent reductions in swimming and swarming movements associated with E. coli flagella showed compound 3′s potential against biofilm development at both MIC and sub-MIC concentrationsNotably, after minimal exposure, compound 3 exhibited a 4-h Post-Antibiotic Effect (PAE) i.e. halting bacterial growth.Compound 3 also demonstrated DNA binding at 64 μg/mL, retarding bacterial DNA movement in agarose gel electrophoresis.In a mouse wound infection model, compound 3 outperformed mupirocin, sterilizing 7 logs CFU of S. aureus in just 2 days, achieving full wound closure by Day 6, and early cessation of pus, showcasing its superior therapeutic efficacy.

01 Jun 2025·Journal of Molecular Structure

Diversity-oriented semi-synthesis of Alantolactone and Isoalantolactone hybrids employing azomethine ylide cycloaddition pathway

Author: Katare, Anil Kumar ; Tabassum, Aliya ; Bharitkar, Yogesh P. ; Bhore, Harshad B. ; Samanta, Jayanta ; Phatake, Ravindra S. ; Abarna, A·Mercy

Alantolactone and isoalantolactone, naturally occurring sesquiterpene lactones, are known for their significant pharmacol. properties, including anti-inflammatory, anticancer, and antimicrobial activities.However, their biol. potential can be further enhanced by structural modification.In this study, we report a diversity-oriented semi-synthesis of novel alantolactone and isoalantolactone hybrids through an azomethine ylide cycloaddition pathway.This efficient process allowed us to create complex and diverse mol. structures.Specifically, we focused on modifying the, α, β-unsaturated exocyclic double bond from butyrolactone core to produce dispirohybrids, including compounds like dispirooxindolo, indanedione, and acenaphthylen-2-one, using amino acids and diketones.The synthesized hybrids were fully characterized using various spectroscopic techniques (1D, 2D-NMR, HRMS, and X-ray diffraction).In silico studies revealed favorable drug-like properties for the synthesized spirocompounds, including ideal physicochem. characteristics, promising pharmacokinetic behavior, excellent oral bioavailability, and minimal toxicity risk.These predictions highlight the potential of these spiroderivatives as strong candidates for further development in drug discovery.This work shows that the azomethine ylide cycloaddition is a useful method for enhancing the chem. and biol. diversity of natural products.

01 Jun 2025·Journal of Biotechnology

Synergistic interaction of AaMYC2 and AaMYC2-LIKE enhances artemisinin production in Artemisia annua L.

Article

Author: Abbas, Nazia ; Kumar, Amit ; Hurrah, Ishfaq Majid ; Mohammad

Artemisinin-based combination therapies recommended by WHO marks Artemisia annua as the only natural source of artemisinin fighting deadly disease, Malaria. In this study, we isolated two transcription factors, AaMYC2 and AaMYC2-LIKE, from A. annua and investigated their role in regulating artemisinin biosynthetic pathway. Our findings depict that both AaMYC2 and AaMYC2-LIKE are transcriptionally active and, when co-transformed in yeast cells, significantly enhance β-galactosidase activity in transactivation assays as compared to their individual transformations. Furthermore, Yeast two-hybrid (Y2H) and Biomolecular fluorescence complementation assays revealed AaMYC2 physically interacts with AaMYC2-LIKE in yeast cells and in the nucleus of onion epidermal cells respectively. Generation of transient transgenic over expression and co-expression lines of AaMYC2 and AaMYC2-LIKE resulted in elevated expression of artemisinin biosynthetic genes and trichome development genes in co-expression lines as compared to individual transgenic lines and wildtype. Importantly, the glandular trichome density and artemisinin content was also significantly higher in co-transformed transgenic lines compared to individual AaMYC2 and AMYC2-LIKE transgenic lines. Conversely, artemisinin content was markedly reduced in AaMYC2-RNAi lines, underscoring the critical role of functional AaMYC2 in synergistic regulation with AaMYC2-LIKE. Altogether the above studies provide valuable insights into the regulatory networks of MYC type bHLH transcription factors in controlling economically and medically important pathway in A. annua.

100 Deals associated with CSIR-Indian Institute of Integrative Medicine

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100 Translational Medicine associated with CSIR-Indian Institute of Integrative Medicine

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Pipeline

Pipeline Snapshot as of 31 Jul 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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