**5. Conclusions**

A novel UPLC-QToF-MS/MS-guided strategy was proposed here for the isolation and characterization of one new depside, decarboxyhomosekikaic acid, along with 13 known metabolites from *Ramalinaconduplicans*—most of them being minor metabolites that were reported on for the first time from this species. In the whole experimental design, UPLC-QToF-MS/MS was selected for multiple purposes, including targeting, finding, profiling, and isolating active constituents. Three hitherto unreferenced compounds were detected in this lichen, with their molecular formulae being deduced from HR-QToF-MS. Although in minute amounts, one isolate could be identified as an additional homosekikaic derivative. The expected major compounds atranorin, usnic acid, salazinic acid, and sekikaic acid were also obtained. However, efforts for isolating, identifying, and testing mainly targeted alkyldepsides- and monoaromatic-related compounds.

These compounds were tested for their antioxidant and α-glucosidase inhibition potential. Most of them, and the crude acetone extract (AE), have displayed antioxidant potential by scavenging ABTS and DPPH radicals and protected DNA from oxidative damage. Five compounds, and particularly hyperhomosekicaic acid, exhibited a comparable or better α-glucosidase inhibition to that of the acarbose standard. On the basis of these results, it is suggested that these lichen substances have a great potential to be used as bioresources or as structural models for novel bioactive candidate compounds. Docking experiments are necessary to document the structure–activities observed in this study along with pharmacomodulation studies to evaluate the antidiabetic properties. Acetone extract unexpectedly showed a comparable effect to that of the Acarbose standard, though it was not sufficient to consider its hypoglycemic activity in the context of the traditional use made of this edible lichen [10].

It should be kept in mind that activities obtained from the crude extract or from any of the active metabolites cannot be claimed to support a preventive or a therapeutic activity as no clinical assay has been carried out to validate an effect with a standardized dosage. Unexpected side effects can occur when preparations differ from the real traditional use, and toxicity trials have to be carried out at once.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/molecules27196720/s1. Detailed Materials and Method. Table S1: LC-QToF-MSE data of compounds from acetone extract of *R. conduplicans*. Physicochemical data of isolated compounds. Figure S1: Authenticate *Ramalina conduplicans*. Figure S2: Shows the spot tests for identification of *Ramalina conduplicans*. Figure S3: Depicts the HPTLC profiles for *R. conduplicans* extract. Figure S4: UPLC-PDA chromatogram of acetone extract of *R. conduplicans*. Figure S5: Total Ion Chromatogram (TIC) of fractions and pure compounds. Figure S6–S46: Spectral data (FTIR spectra, HRESIMS, MS/MS spectra and fragmentation pattern, 1H & 13C NMR, DEPT, HSQC, DQF-COSY and NOESY spectra) of compounds **1**–**14**, salazinic acid, usnic acid and atronarin. Figure S47: TIC of *R.conduplicans*. Figure S48: Common fragmentation of depsides. Figure S49. Invitro DNA damage assay.

**Author Contributions:** K.S.B., the biologist A.K.T. and J.B. conceived and designed the experiments; T.K.K., B.S. and K.S.B. performed the experiments; K.S.B., F.L.D. and J.B. analyzed the data; A.M.R. and S.M. contributed to the material identification reagents/materials and tools; A.A. and K.A. performed in vitro biological experiments and analyzed data; B.S., A.K.T., K.S.B. and J.B. wrote/revised the paper. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding authors.

**Acknowledgments:** This research was performed as a part of the Indo-French IRP 'Natural Products and Synthesis for Affordable Health' and acknowledgments are due to CSIR (India) and CNRS (France). Authors thank to Director, IICT for his constant encouragement and support and to S. Labarre for English revision. B.S. thanks CSIR for fellowship program and financial support. IICT communication no. IICT/Pubs./2022/082.

**Conflicts of Interest:** The authors declare no conflict of interest.

**Sample Availability:** Samples of the compounds **1**–**14** are available from the authors, and the samples were deposited in the institutional depository.
