An Ethnopharmacological Survey on Medicinally Important Plants of Genus Salvia.

Lamiaceae (Labiatae) is a medicinally significant plant family featuring key species like Salvia aegyptiaca, S. cabulica, S. coccinea, S. glutinosa, S. officinalis, S. haematodes, S. hians, S. lanata, S. macrosiphon, S. moorcroftiana, S. spinosa, S. sclarea, and S. plebeia. These species exhibit diverse pharmacological activities attributed to essential oils and phytochemi-cals, including antioxidant, antiasthmatic, antitumor, anti-inflammatory, analgesic, etc. This re-view covers extensive phytomedicinal aspects of some important plants of the genus Salvia.

Extensive Multiple 2D-/3D-QSAR Modeling, Molecular Docking and Pharmacophoric Approaches for Piperazinylquinoline Derivatives as Respiratory Syncytial Virus Fusion Inhibitors.

BACKGROUND: The human respiratory syncytial virus (RSV) is responsible for causing upper and lower respiratory tract infections in young children. RSV Fusion (F) protein is a surface glycoprotein that facilitates virus entry into host cells. Thus, newer designing of RSV Fusion (F) protein inhibitors is required on an urgent basis. METHODS: In the present study, we have developed statistically robust. Quantitative structure-activity relationship (QSAR) models for the effective designing of newer analogues of piperazinylquinoline derivatives (H1-H12). RESULTS: Our developed models were retained with high statistical parameters (R2 > 0.6 and Q2 > 0.5). Our developed pharmacophore, model (AADHRR_2) (indicating that two hydrogen bond acceptors, one hydrogen bond donor, one hydrophobic group, and two aromatic rings) is crucial for retaining the activities of piperazinylquinoline derivatives against RSV. Moreover, docking analysis of 12 new analogues on RSV pre-F in complex with 5C4 Fab (PDB ID: 5W23) and post-F trimeric protein (PDB ID: 3RRR) suggested higher affinities of these molecules against studied targets with good docking scores. CONCLUSION: Thus, one can implement developed QSAR models, docking analogy and Pharmacophore models for identifications of potent leads for designed molecules as RSV Fusion (F) protein inhibitors.

L-Proline: A Versatile Organo-Catalyst in Organic Chemistry.

BACKGROUND: L-proline is a natural amino acid having secondary amine functionality and acts as a bifunctional catalyst (organo-catalyst). The amino-functional group acts as Lewis base type while carboxylic acids act as Brønsted acid type catalysts. It catalyzed different asymmetric syntheses, including known reactions such as Aldol condensation, Mannich reaction, Michael Addition, Knoevenagel condensation, Hantzsch synthesis, OXA-Michael Henry tandem, Ullmann reactions, Wieland-Miescher ketone synthesis, Robinson annulation, Biginelli reaction, α- amination. It is also an essential catalyst for synthesizing heterocyclic skeletons such as coumarin, spiro-oxindoles, imidazoles, benzimidazoles, quinoxalines, podophyllotoxin, benzothiazoles, isoxazolidines, phenothiazines, aziridine, indole, 1,5-benzodiazepines, pyridine, and quinazolines. OBJECTIVE: In this review, we had the objective to critically summarize the use of proline and proline derivatives as catalysts of multicomponent reactions performed in various media and leading to synthetically and biologically relevant heterocycles, a very important class of compounds that constitutes over 60% of drugs and agrochemicals. METHODS: All scholarly articles for L-Proline catalyzed reactions were retrieved from ScienceDirect, Google Scholar , PubMed, etc. Results and Conclusion: Given the importance of L-Proline based reactions, it has been observed to have tremendous applications in organic chemistry. It can also act as a 'Green catalyst'.

Synthesis, Characterization, 'ADMET-SAR' Prediction, DPPH Assay, and Anti-Mycobacterium Study of 4-[(substituted benzyl) amino]benzo hydrazides and its Hydrazones as the Acyl-CoA Carboxylase, AccD5 Inhibitors.

BACKGROUND: Hydrazide-hydrazone derivatives have shown diverse biological activities, such as antitubercular (anti-TB), antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal actions. OBJECTIVES: Hydrazide-hydrazones contain azomethine (-NH-N=CH-) group connected with carbonyl group and are believed to be responsible for various pharmaceutical applications. They aid in the synthesis of different five-membered heterocyclic systems, such as oxadiazole, triazoles, etc. Methods: In the present study, various hydrazines/hydrazones were synthesized starting from 4- amino benzoic acid derivatives. Structures of all 9 newly synthesized compounds (6a-6d and 8a- 8e) were further characterized by using various spectroscopic methods, such as 1H-NMR (Nuclear Magnetic Resonance), FT-IR (Fourier-transform infrared spectroscopy), Gas chromatographymass spectrometry (GC-MS), etc. Furthermore, molecular docking analysis against the acyl-CoA carboxylase, AccD5 (PDB ID: 2A7S), was also carried out using the Glide module, which depicted good binding scores than standard drugs. The anti-tuberculosis activity of all the hydrazides and hydrazones (6a-6d and 8a-8e) were evaluated against the Mycobacterium tuberculosis H37 RV strain using the Alamar-Blue susceptibility (MABA) test. The activity was expressed as the minimum inhibitory concentration (MIC) in µg/mL values. The antioxidant activity was also carried out using a DPPH assay. RESULTS: Our findings demonstrated highly encouraging in-vitro results (MABA assay, MIC: 1.2 µg/mL) of hydrazones as depicted by good antimycobacterial activity. The antioxidant results showed a moderate to a good percentage of DPPH inhibition. Our in-silico ADMET analysis further suggested good pharmacokinetic and toxicity-free profiles of synthesized analogues (6a-6d and 8a-8e). CONCLUSION: Our results signify hydrazones/hydrazines as potential hit candidates against the future developments of potent and safer anti-TB agents.

Green Surfactants (Biosurfactants): A Petroleum-Free Substitute for Sustainability-Comparison, Applications, Market, and Future Prospects.

Surfactants are a group of amphiphilic molecules (i.e., having both hydrophobic and hydrophilic domains) that are a vital part of nearly every contemporary industrial process such as in agriculture, medicine, personal care, food, and petroleum. In general surfactants can be derived from (i) petroleum-based sources or (ii) microbial/plant origins. Petroleum-based surfactants are obvious results from petroleum products, which lead to petroleum pollution and thus pose severe problems to the environment leading to various ecological damages. Thus, newer techniques have been suggested for deriving surfactant molecules and maintaining environmental sustainability. Biosurfactants are surfactants of microbial or plant origins and offer much added advantages such as high biodegradability, lesser toxicity, ease of raw material availability, and easy applicability. Thus, they are also termed "green surfactants". In this regard, this review focused on the advantages of biosurfactants over the synthetic surfactants produced from petroleum-based products along with their potential applications in different industries. We also provided their market aspects and future directions that can be considered with selections of biosurfactants. This would open up new avenues for surfactant research by overcoming the existing bottlenecks in this field.

Synthesis, Molecular Docking, and In vitro Antimycobacterial Studies on N'-arylidene-4-nitrobenzohydrazides.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is an organism that causes tuberculosis (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones- hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication. OBJECTIVES: We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature. MATERIALS AND METHODS: All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial activity against H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors. RESULTS: Among all tested molecules, 3i (MIC: 50 µg/mL) and 3b (MIC: 50 µg/mL) were found to be the best ligands for further development of new anti-TB drug. We found that our proposed molecules have higher docking scores, corresponding standard anti-TB agents, such as ciprofloxacin and isoniazid. Synthesized compounds were found to have druglikeness properties when tested with Lipinski's filter for drug-likeness. CONCLUSION: Our current study proposes N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for development into active lead molecules.

Synthesis, In silico and In vitro Analysis of Hydrazones as Potential Antituberculosis Agents.

Tuberculosis (TB) is a major cause of mortality and illness as reported by the W.H.O in 2019. The WHO report also mentioned the fact that about 10.0 million people fell ill with tuberculosis in the year 2018. Hydrazide-hydrazones having azomethine group (-NH-N=CH-) connected with carbonyl group is reported for the number of bioactivities like anti-inflammatory, anticonvulsant, anticancer, antiviral and antiprotozoal. OBJECTIVE: The objective of our current study is to design and synthesise more potent hydrazide- hydrazones, containing anti-tubercular agents. METHODS: In the current study, we synthesized 10 hydrazones (3a-3j) by stirring corresponding benzohydrazides (2) with substituted aldehydes (1a-j) in ethanol as a solvent and acetic acid as a catalyst at room temperature. All synthesized compounds were characterized by various spectroscopic techniques including elemental analysis, ultraviolet-visible spectroscopy, fluorescence, fourier- transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Compounds (3a-3j) were tested for in vitro anti-TB activity using Microplate Alamar Blue Assay (MABA). RESULTS: All our synthesized compounds (3a-3j) were found to be potent against Mycobacteria tuberculosis (H37RV strain) with MIC (minimum inhibitory concentrations) values of 3.125-50 µg/mL. The hydrazide CO-NH protons in (3a-j) compounds are highly deshielded and showed broad singlet at 9.520-9.168 ppm. All the compounds were found to have more intense emission in the 416 - 429 nm regions and strong absorption in the regions of 316 - 327 nm. Synthesized compounds were also tested for in silico analysis using different software for their Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis. All the compounds were found to be in silico non-carcinogenic. CONCLUSION: It will be worth saying that our in silico and in vitro approaches used in the current study will become a guide for medicinal chemists to make structural modifications and synthesize more effective and potent hydrazone containing anti-tubercular agents.

Synthesis, admetSAR Predictions, DPPH Radical Scavenging Activity, and Potent Anti-mycobacterial Studies of Hydrazones of Substituted 4-(anilino methyl) benzohydrazides (Part 2).

BACKGROUND: For the past several decades, the presence of tuberculosis (TB) is being remarked as the most common infectious disease leading to mortality. OBJECTIVE: Hydrazone containing azometine group (-NHN=CH-) compounds have been reported for a broad range of bioactivities such as antiplatelet, analgesic, anti-inflammatory, anticonvulsant, antidepressant, antimalarial, vasodilator, antiviral, and antimicrobial, etc. Methods: For the synthesis of compounds (4a-4d) and (6a-6e), aromatic amines were treated with methyl terephthalaldehydate in methanol, giving Schiff's bases, followed by reductive amination and further treatment with hydrazine hydrate gave acid hydrazides (4a-4d). These acid hydrazides were then treated with different aromatic aldehydes to yield hydrazones (6a-6d). All the synthesized compounds were subjected to FT-IR, NMR, and UV spectroscopic characterization. RESULTS: Compounds (4a-4d) and (6a-6e) were found to have highly potent activity against Mycobacteria tuberculosis (Vaccine strain, H37 RV strains): ATCC No- 27294 (MIC:1.6-6.25 µg/mL) than standard anti-TB drugs. The compounds exhibited good radical scavenging potentials(0- 69.2%), as checked from DPPH protocol. All compounds also demonstrated good in-silico ADMET results. CONCLUSION: The current study revealed promising in vitro anti-tuberculosis and anti-oxidant profiles of hydrazide-hydrazone analogues.

Synthesis, Spectroscopic, In-vitro and Computational Analysis of Hydrazones as Potential Antituberculosis Agents: (Part-I).

BACKGROUND: Since the last few decades, the healthcare sector is facing the problem of the development of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) infections all over the world. Regardless of the current healthcare progress for the treatment of mycobacterial infections, we are still unable to control addition of every year 9 million new cases of tuberculosis (TB). OBJECTIVE: We had an objective to synthesize some novel hydrazones, which were further subjected to characterization, Photoluminescence study, in vitro anti-mycobacterium testing and in silico ADMET predictions. METHODS: Some new hydrazone derivatives have been successfully prepared by the condensation reaction in the present study. All the compounds were characterized by using FTIR, NMR, UV, Fluorescence spectroscopic techniques. RESULTS: All our newly synthesized compounds showed strong electronic excitation at 292.6 - 319.0 nm and displayed more intense emissions in the 348 - 365 nm regions except compound 3i. The newly synthesized hydrazones 3a, 3b, 3f and 3g were found to be the most active compounds and showed MIC (Minimum inhibitory concentrations) values of 12.5 µg/mL. CONCLUSION: In the realm of development of more potent, effective, safer and less toxic antituberculosis agents; our current study would definitely help the medicinal chemists to develop potent analogues containing hydrazine motifs in them.

Synthesis, SAR, Molecular Docking and Anti-Microbial Study of Substituted N-bromoamido-2-aminobenzothiazoles.

BACKGROUND: Benzothiazoles are reported to have bioorganic and pharmaceutical chemistry applications. INTRODUCTION: A series of substituted N-bromoamido-2-aminobenzothiazoles was synthesized from substituted anilines via 2-aminobenzothiazoles and it was further evaluated for its antimicrobial activity. METHODS: All the newly synthesized compounds were characterized by FT-IR, NMR and mass spectra and purity profiles were studied by HPLC analysis. The antimicrobial testing (MIC determination) was newly performed with agar micro-broth dilution method for these analogs. RESULTS: Among the synthesized compound 3b showed the highest activity with MIC value of 3.12 µg/mL against Bacillus, E. coli, S. aureus and Klebsiella and 6.25 µg/mL against C. albicans. The ADME properties as calculated by using Qikprop were found within acceptable range. Derivatives shows a good-moderate binding affinity towards target Cytochrome P450 14 alpha-sterol demethylase (CYP51) (PDB ID: 1EA1). CONCLUSION: Our in-silico and in-vitro studies on a series of substituted aminobenzothiazoles may be helpful for further designing of more potent antimicrobials in future.

Synthesis, SAR, In silico Appraisal and Anti-Microbial Study of Substituted 2-aminobenzothiazoles Derivatives.

BACKGROUND: Antimicrobial resistance is a major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2- (4-(6-fluorobenzo[d]isoxazol-3-yl) piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3- (piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. METHODS: All the synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. RESULTS: The compounds 3d and 3h showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. CONCLUSION: Our current study would definitely pave the new way of designing and synthesis of more potent 2-aminobenzothiazoles derivatives.

Synthesis and Anti-mycobacterium Study on Halo-substituted 2-aryl oxyacetohydrazones.

BACKGROUND: The treatment of multiple-drug-resistant tuberculosis (MDR-TB) with currently available marketed drugs remains a global health concern. The cases of resistant tuberculosis patients are increasing day by day. OBJECTIVE: The objective of this study is to highlight the need of developing shorter, simpler and tolerable drug regimens. METHODS: In the present study, we synthesized various halo-substituted 2-aryloxyacetohydrazones via a series of reactions from halo-substituted phenols. All the compounds were characterized by using various spectroscopic methods, such as NMR, FT-IR, UV spectroscopy, etc. Results: All the synthesized hydrazones showed theoretically good interactions with enzyme enoyl reductase (pdb id: 4tzk). All the synthesized compounds (5a-5o) showed moderate to good activity (3.125-100 µg/mL) against Mycobacteria tuberculosis, H37RV strain. CONCLUSION: Our results would pave a new way for the development of more effective Anti-TB agents in the future.