Volume 8 Issue 3 Article 24

Piperine: A Mini Review on its Pharmacological Profile and Synthetic Derivatives

Authors: Mohd. Javed Naim1 & Javed Ahamad2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan Region, Iraq
2Department of Pharmacognosy, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan Region, Iraq

Abstract: Piperine, known for its vast biological profile, is obtained from black pepper (Piper nigrum, Family: Piperaceae) which is one of the most commonly used spice in major parts of the world and is known for its pungent taste. Piperine is also found to act as an important bioenhancer by increasing the bioavailability of drug molecules and reducing their dosing frequency and dosage. This review article aims at providing various biological activities exhibited by piperine and its numerous synthetic derivatives in order to get some potential lead molecule for future drug discovery.

Keywords: Piperine, Piper Nigrum, Piper longa, Anticancer, Antibacterial, Bioenhancer

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Doi: 10.23918/eajse.v8i3p308

Published: January 5, 2023

References

Ali, Y., Alam, M.S., Hamid, H., Husain, A., Bano, S., Dhulap, A., Kharbanda, C., Nazreen, S. and Haider, S. (2015). Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents. European Journal of Medicinal Chemistry, 92, 490-500.

Amala, R., Zhixiu, Li. (2013). Use of Piperine and Analogues Thereof in the Prevention of Skin Cancer. CA 2735844.

Chavarria, D., Fernandes, C., Silva, V., Silva, C., Gil-Martins, E., Soares, P., Silva, T., Silva, R., Remiao, F.,
Oliveira, P.J. and Borges, F. (2020). Design of novel monoamine Oxidase-B inhibitors based on piperine scaffold: Structure-activity-toxicity, drug-likeness and efflux transport studies. European Journal of Medicinal Chemistry, 185, 111770.

Chopra, B., Dhingra, A.K., Kapoor, R.P. and Prasad, D.N. (2016). Piperine and its various physicochemical and biological aspects: A review. Open Chemistry Journal, 3(1).

Da Silva Ferreira, W., Freire-de-Lima, L., Saraiva, V.B., Alisson-Silva, F., Mendonça-Previato, L., Previato, J.O.,

Echevarria, A. and de Lima, M.E.F. (2008). Novel 1, 3, 4-thiadiazolium-2-phenylamine chlorides derived from natural piperine as trypanocidal agents: chemical and biological studies. Bioorganic & medicinal chemistry, 16(6), 2984-2991.

Domany, G., Horvath, C., Farkas, S., Bartane, S.G., Nagy, J., Kolok, S., Kovacsne, B.E., Borza, I., Vago, I., Bielik, Attila., Ignaczne, S.G., Keseru, G. (2004). Piperidine derivatives as nmda receptor antagonists. WO2003010159A8.

Eigenmann, D.E., Dürig, C., Jähne, E.A., Smieško, M., Culot, M., Gosselet, F., Cecchelli, R., Helms, H.C.C., Brodin, B., Wimmer, L. and Mihovilovic, M.D. (2016). In vitro blood–brain barrier permeability predictions for GABAA receptor modulating piperine analogs. European Journal of Pharmaceutics and Biopharmaceutics, 103, 118-126.

Elimam, D.M., Elgazar, A.A., Bonardi, A., Abdelfadil, M., Nocentini, A., El-Domany, R.A., Abdel-Aziz, H.A., Badria, F.A., Supuran, C.T. and Eldehna, W.M. (2021). Natural inspired piperine-based sulfonamides and carboxylic acids as carbonic anhydrase inhibitors: Design, synthesis and biological evaluation. European Journal of Medicinal Chemistry, 225, 113800.

Ferreira, C., Soares, D.C., Barreto-Junior, C.B., Nascimento, M.T., Freire-de-Lima, L., Delorenzi, J.C., Lima, M.E.F., Atella, G.C., Folly, E., Carvalho, T.M.U. and Saraiva, E.M. (2011). Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania amazonensis. Phytochemistry, 72(17), 2155-2164.

Ferreira, R.C., Batista, T.M., Duarte, S.S., Silva, D.K.F., Lisboa, T.M.H., Cavalcanti, R.F.P., Leite, F.C., Mangueira, V.M., de Sousa, T.K.G., de Abrantes, R.A. and da Trindade, E.O. (2020). A novel piperine analogue exerts in vivo antitumor effect by inducing oxidative, antiangiogenic and immunomodulatory actions. Biomedicine & Pharmacotherapy, 128, 110247.

Joardar, N., Shit, P., Halder, S., Debnath, U., Saha, S., Misra, A.K., Jana, K. and Babu, S.P.S. (2021). Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: an in vitro mechanistic approach. Free Radical Biology and Medicine, 169, 343-360.

Khom, S., Strommer, B., Schöffmann, A., Hintersteiner, J., Baburin, I., Erker, T., Schwarz, T., Schwarzer, C., Zaugg, J., Hamburger, M. and Hering, S. (2013). GABAA receptor modulation by piperine and a non-TRPV1 activating derivative. Biochemical pharmacology, 85(12), 1827-1836.

Kozukue, N., Park, M.S., Choi, S.H., Lee, S.U., Ohnishi-Kameyama, M., Levin, C.E. and Friedman, M. (2007). Kinetics of Light-Induced cis− trans isomerization of four piperines and their levels in ground black peppers as determined by HPLC and LC/MS. Journal of agricultural and food chemistry, 55(17), pp.7131-7139.

Majeed, M., Badmaev, V. (2000). Process for making high purity piperine for nutritional use. US6054585A.

Majeed, M., Badmaev, V., Rajendran, R. (1998). Use of piperine as a bioavailability enhancer. US5744161A.

Parthasarathy, V.A., Chempakam, B. and Zachariah, T.J. eds. (2008). Chemistry of spices. Cabi.

Phull, M.S., Rao, D.R., Malhotra, G., Birari, D.R., Desai, S.V. (2019). Process for the preparation of piperine. WO2019073491A1.

Pruthi, J.S. (1999). Quality assurance in spices and spice products, modern methods of analysis.

Ravindran, P.N. ed. (2000). Black pepper: Piper nigrum. CRC press.

Shahbazi, S., Zakerali, T., Frycz, B.A. and Kaur, J. (2020). The critical role of piperamide derivative D4 in the regulation of inflammatory response by the microglia and astrocytic glial cells. Biomedicine & Pharmacotherapy, 132, 110895.

Sivashanmugam, A. and Velmathi, S. (2022). Synthesis and Characterization of Piperine Amide analogues: Their In-silico and invitro analysis as Potential antibacterial agents. Results in Chemistry, 100369.

Sozzi, G.O., Peter, K.V., Babu, K.N. and Divakaran, M. (2012). Capers and caperberries. In Handbook of herbs and spices, 193-224. Woodhead Publishing.

Tantawy, A.H., Farag, S.M., Hegazy, L., Jiang, H. and Wang, M.Q. (2020). The larvicidal activity of natural inspired piperine-based dienehydrazides against Culex pipiens. Bioorganic Chemistry, 94, 103464.

Tiwari, A., Mahadik, K.R. and Gabhe, S.Y. (2020). Piperine: A comprehensive review of methods of isolation, purification, and biological properties. Medicine in Drug Discovery, 7, 100027.

Wang, L., Cai, X., Shi, M., Xue, L., Kuang, S., Xu, R., Qi, W., Li, Y., Ma, X., Zhang, R. and Hong, F. (2020). Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson’s disease via the activation of Nrf2/keap1 pathway. European Journal of Medicinal Chemistry, 199, 112385.

Wimmer, L., Schönbauer, D., Pakfeifer, P., Schöffmann, A., Khom, S., Hering, S. and Mihovilovic, M.D. (2015). Developing piperine towards TRPV1 and GABA A receptor ligands–synthesis of piperine analogs via Heck-coupling of conjugated dienes. Organic & biomolecular chemistry, 13(4), 990-994.

Yang, X., Ji, J., Liu, C., Zhou, M., Li, H., Ye, S. and Hu, Q. (2020). HJ22, a Novel derivative of piperine, attenuates ibotenic acid-induced cognitive impairment, oxidative stress, apoptosis and inflammation via inhibiting the protein-protein interaction of Keap1-Nrf2. International Immunopharmacology, 83, 106383.

Yang, X., Zhi, J., Leng, H., Chen, Y., Gao, H., Ma, J., Ji, J. and Hu, Q. (2021). The piperine derivative HJ105 inhibits Aβ1–42-induced neuroinflammation and oxidative damage via the Keap1-Nrf2-TXNIP axis. Phytomedicine, 87, 153571.