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Increased effectiveness and decreasing toxicity are prime objectives in drug research. Overwhelming evidence suggests the use of appropriate combination therapy for the better efficacy of drugs owing to their synergistic profile. Dietary active constituents play a major role in health outcomes. Therefore, it is possible to increase the effectiveness of the drug by combining contemporary medication with active natural/semi-synthetic constituents. One such dietary constituent, caffeic acid (CA), is a by-product of the shikimate pathway in plants and is a polyphenol of hydroxycinnamic acid class. Extensive research on CA has proposed its efficacy against inflammatory, neurodegenerative, oncologic, and metabolic disorders. The synergistic/additive effects of CA in combination with drugs like caffeine, metformin, pioglitazone, and quercetin have been reported in several experimental models and thus the present review is an attempt to consolidate outcomes of this research. Multi-target-based mechanistic studies will facilitate the development of effective combination regimens of CA.

Purpose: Alzheimer's is a disease affecting mostly the Older population leading to the deterioration of cognitive capabilities. The protective effect of Caffeic acid in Colchicineinduced dementia was evaluated in the current study. Materials and Methods: Colchicine was administered intracerebroventricularly (ICV) to the lateral ventricle of the brain (at the coordinates 0.8 mm posterior to bregma, 1.8 mm lateral to the sagittal suture, 3.6 mm below the cortical surface) using robotic stereotaxic apparatus that results in Alzheimer's type sporadic dementia. Caffeic acid at the dose of 50 mg/kg p.o, was administered daily for 25 days starting four days before the colchicine injection and evaluated for its neuroprotective activity. The spatial memory of animals was evaluated using Morris water maze followed by biochemical estimations of acetylcholinesterase and antioxidant markers in the hippocampal and frontal cortex region of the brain. Results: Intracerebroventricular injection of colchicine in rat brain resulted in decreased cognitive abilities as evident in escape latency and average speed of the retention trial. Significant changes in the escape latency were noted in Caffeic acid-treated group. The level of acetylcholinesterase and antioxidant markers like glutathione, catalase, lipid peroxidation, superoxide dismutase were significantly changed in the hippocampal region of the rats but not in the frontal cortex region in the caffeic acid treatment groups. Conclusion: The current study provides evidence for the neuroprotective and antioxidative potential of caffeic acid in intracerebroventricularly injected Colchicine-induced sporadic model of AD.

Tuberculosis is the "Achilles heel" of the human immunodeficiency (HIV) ministration.HIV-positive people are 16-27 times more prone to contract tuberculosis. But the adverse interaction between antiretroviral drugs and antitubercular drugs has made it necessary to look for a single drug regimen for HIV-TB coinfection. Piperidine derivatives have been reported as anti-HIV and anti-TB agents. This inspired us to design, synthesize, and characterize a series of 3,5-bis(furan-2-ylmethylidene)piperidin-4-substituted imines (R1-R25) and these were further screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv and anti-HIV activity. Molecular docking studies showed energetically favorable binding interactions with both EACP reductase (1ZID.pdb) and reverse-transcriptase (1REV.pdb) targets. The compounds R7, R12, R17, R18, R19, R20 were found to be more potent as anti-TB agents than ethambutol (MIC 3.125 μg/ml). Compound R7 was found to be moderately active with an IC 50 of 2.1 ± 0.04 μM in multicycle infection assays, in comparison with the standard drug, zidovudine (IC 50 = 5.7 ± 0.04 nM), used as anti-HIV drug. The cytotoxicity assay was done on Vero, MT-2, and TZM-bl cells to assess the safety of these compounds and they were found to be safe. From the above results, R7 seems to be a promising lead for anti-HIV and anti-TB activity.

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