Production and Characterization of Novel Board-spectrum Antimicrobial 5-butyl-2-pyridine carboxylic acid from Aspergillus fumigatus nHF-01

Objectives: The present study aims to report on the production optimization, purification, and characterization of structural and functional attributes of a novel broad-spectrum antibacterial compound produced by Aspergillus fumigatus nHF-01 (GenBank Ac. No. MN190286).Materials and Methods: The culture conditions were optimized by using rigorous culture-set preparation considering various abiotic and biotic factors for a higher amount of antimicrobial production. The produced antimicrobial was solvent extracted and purified by preparative TLC and HPLC methods followed by characterization using UV-Vis, FT-IR, ESI-MS, and 1H-NMR spectroscopy. The MIC and MBC of the antimicrobials were determined against a set of Gram-positive and Gram-negative human pathogenic bacteria. The mode of action on cellular morphology and integrity were determined by LDH and SEM studies. Its biofilm-inhibition properties and synergistic activity with antibiotics were studied. The possible cytotoxic effect on human cell lines was also tested by MTT assay. The putative target site of action was evaluated through in silico molecular docking study. Results: The micro-fungus A. fumigatus nHF-01 produced the maximum antibacterial compound while grown in a combination of 2% MEB (w/v) and 4% YE (w/v) at pH 6.0 and 20 °C temperature with 100 rpm agitation for ten days. The DCM extractable crude compound has a potent growth inhibition against the target human food and topical pathogenic bacteria at a 15 mg/ml concentration and is stable up to 100 °C. The spectroscopic studies confirmed the antimicrobial compound as 5-butyl-2-pyridine carboxylic acid with MIC values from 0.069±0.0034 to 1.12±0.052 mg/ml and from 8.925±0.39 to 17.85±0.78 mg/ml; and MBC values from 8.925±0.40 to 17.85±0.776 mg/ml and from 0.069±0.0034 to 0.139±0.0065 mg/ml against human pathogenic Gram-positive and Gram-negative bacteria, respectively. A concentration of 0.139 and 17.85 mg/ml decreased the viability sharply within 15 min of the incubation period with the gradual increase in LDH activity, indicating a robust bactericidal and lytic mode of action. The time-kill kinetics study shows that at a 17.85 mg/ml dose (i.e. MBC), the compound caused zero viability of E. coli and S. epidermidis cells from the initial log CFU/ml 5.78 after 15 h of treatment. It caused a remarkable change in morphology like the formation of blebbing, notch, rupture of the entire cell walls, and entire dissolution of cell integrity at a concentration of 4 µg/ml and 129 µg/ml. It had cytotoxicity against the tested human lung carcinoma A549 cell line. It showed a notable antibiofilm activity at 20 µg/ml and 4 µg/ml comparable to the standard antibiofilm drug usnic acid 10 µg/ml and 64 µg/ml against E. coli and B. cereus. It had a synergistic activity with streptomycin, whereas ciprofloxacin and vancomycin showed additive effects. It showed the highest binding affinities with Quinol-Fumarate Reductase (1l0v), a respiratory enzyme. Conclusion: Thus, the above findings can be concluded that the strain A. fumigatus nHF-01 produces a novel broad-spectrum antimicrobial compound 5-butyl-2-pyridine carboxylic acid with potent bactericidal activity against human food and topical pathogenic bacteria. This is the first report of such a compound from the A. fumigatus.

Synthesis and Anticancer Perspective of Pyridopyrimidine Scaffold - An Overview

The core pyridopyrimidines are gaining interest in organic and heterocyclic chemistry in recent days, as this scaffold acts as a building block because of its wide range of biological and pharmacological applications like anticancer, antimicrobial, fungicidal, antiviral, CNS, antibacterial, and anti-inflammatory properties. This review mainly emphasizes the evolution in anticancer properties of pyridopyrimidines since 2008 especially the method of synthesis and anticancer activity of synthesized compounds with reporting of active anticancer scaffolds. Important starting materials which are widely used for the synthesis are 2-thioxopyrimidine, ethyl 2-cyanoacetate, 2-amino-3-cyano-4-trifluoromethyl-6-phenyl-pyridine, 2-amino-4,6-disubstituted nicotinonitrile, 2-chloro-3-pyridine carboxylic acid, in which 2-thioxopyrimidine is found to be mostly employed in the synthesis. Pyridopyrimidines which are synthesized from different starting materials, in which the more active compounds are reported here which may help in further discovery/ development of novel molecules.

Ruthenium-catalyzed Asymmetric Dehydrative Allylic Cyclization of Chalcogen 5-Membered Heteroaromatics

The asymmetric dehydrative intramolecular allylation reactions of furan and thiophene were performed using a cationic cyclopentadienyl-ruthenium (CpRu) complex of a chiral pyridine carboxylic acid, namely Cl-Naph-PyCOOH. Both furan and thiophene tethered with an allylic alcohol gave the corresponding bicyclic compounds in high yields and enantioselectivities using 0.1–5 mol% of catalyst. The reaction was found to proceed via a similar enantioface selection method mechanism to that previously reported by our group, which involved halogen and hydrogen bond formation, in addition to the generation of an intermediate σ-allyl complex.

Micropropagation of Tulip via Somatic Embryogenesis

An effective method of tulip regeneration via somatic embryogenesis (SE) was developed. Explants, flower stem slices excised from cooled bulbs were incubated in darkness on MS modified media containing auxins alone (2,4-dichlorophenoxyacetic acid—2,4-D, 1-naphthalene acetic acid—NAA and 4-amino-3,5,6-trichloro-2-pyridine carboxylic acid—picloram) or combined with thidiazuron (TDZ) at 0.1 and 0.5 mg L−1. Yellowish-white callus with a granular structure was developed in the presence of all auxins on the cut surface from the tissues of the vascular bundles. From this, lines of embryogenic calli were derived. The addition of TDZ to the medium with auxins significantly stimulated somatic embryo formation. Cyclic and the most intensive proliferation of embryogenic callus as well as embryo formation was obtained in the presence of 2,4-D at 0.1 mg L−1 combined with TDZ at 0.5 mg L−1. Addition of proline enhanced either callus proliferation rate or frequency of embryo formation. The best quality embryos with cotyledons longer than 10 mm able to form bulbs were recorded when TDZ was replaced with 6-benzylaminopurine (BAP) at the concentration of 0.1 mg L−1. Histomorphology showed that the development of somatic embryos could have either external or internal origins. Embryos of external origin were initiated by cell division on the edge of embryogenic calli. Embryos of internal origin resulted from the division of parenchyma cells inside the tissue. Embryonic cells were characterized by their small volume, regular shape, dense cytoplasm and large nuclei. The globular embryos were covered by a distinct layer of periderm. Then, the embryos developed into structures having leaf-shaped cotyledons with a procambial strand and a sideward-orientated meristem of the vegetative apex (stolon). Cotyledon embryos did not show vascular connections with the parent tissue, and they did not develop embryonic roots.

Relative activity comparison of aminocyclopyrachlor to pyridine carboxylic acid herbicides

The pyridine carboxylic acid (PCA) herbicide family can exhibit differential activity within and among plant species, despite molecular resemblances. Aminocyclopyrachlor (AMCP), a pyrimidine carboxylic acid, is a recently discovered compound with similar use patterns to those of the PCA family; however, relative activity among PCAs and AMCP is not well understood. Therefore, the objective of this study was to quantify relative activity among aminopyralid, picloram, clopyralid, triclopyr, and AMCP in canola, squash, and okra using dose-response whole-plant bioassays. Clopyralid was less active than all other herbicides in all species and did not fit dose-response models. Aminopyralid and picloram performed similarly in squash (ED50 = 21.1 and 23.3 g ae ha−1, respectively). Aminopyralid was 3.8 times and 1.7 times more active than picloram in canola (ED50 = 60.3 and 227.7 g ha−1, respectively) and okra (ED50 = 10.3 and 17.3 g ha−1, respectively). Triclopyr (ED50 = 37.3 g ha−1) was more active than AMCP (ED50 = 112.9 g ha−1) and picloram in canola. Aminocyclopyrachlor (ED50 = 6.6 g ha−1) and triclopyr (ED50 = 7.8 g ha−1) were more active in squash than aminopyralid and picloram. In okra, AMCP (ED50 = 14.6 g ha−1) and aminopyralid (ED50 = 10.3 g ha−1) performed similarly but were more active than triclopyr (ED50 = 88.2 g ha−1). Herbicidal activity among AMCP and PCAs was vastly different despite molecular similarities that could be due to variable target-site sensitivity among species.

Synthesis, Crystal Structures, and Magnetic Properties of Three Cobalt(II) Coordination Polymers Constructed from 3,5-Pyridinedicarboxylic Acid or 3,4-Pyridinedicarboxylic Acid Ligands

Three 2D new coordination polymers Co2(L1)2(1,10-Phenanthroline)2(DMF)0.5(H2O) (1), (H2L1 = Pyridine-3,5-dicarboxylic acid) Co(L1)(2,2-bipyridine) (2), and Co(L2)(2,2-bipyridine) (DMF) (3) (H2L2 = Pyridine-3,4-dicarboxylic acid) were synthesized through a solvothermal reaction of cobalt nitrate and pyridine carboxylic acid ligand with the auxiliary ligand (1,10-Phenanthroline or 2,2-bipyridine). They were characterized by X-ray diffraction and elemental analysis, infrared spectroscopy, thermogravimetry analysis, and magnetism. Compounds 1–3 featured 2D hexagonal (6,3) networks which linked into 3D supramolecular architectures through π–π interaction. In addition, compounds 1 and 2 showed the antiferromagnetic exchange interactions, and the magnetic property of compound 3 exhibited ferromagnetic exchange interactions.