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Synthesis and anthelmintic activity of some novel (E)-2-methyl/propyl-4-(2-(substitutedbenzylidene)hydrazinyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines

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Abstract

A series of some novel (E)-2-methyl/propyl-4-[(2-(substitutedbenzylidene)hydrazinyl]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines was synthesized and characterized by adopting an appropriate synthetic scheme. The effect of electron withdrawing and electron donating groups at the aromatic ring in presence of methyl and propyl substituents at the 2-position of the scaffold was evaluated for anthelmintic activity against adult Indian earthworms (Pheretima posthuma). Among 2-methyl-thieno[2,3-d]pyrimidine analogs, compounds with electron donating methoxy group either at para-position or at meta and para-positions of the aromatic ring showed potent anthelmintic activity at 100 μg/ml (284 and 261.8 μM concentrations) for compounds 5g and 5h with a mean paralytic time of 2.32, 2.22 min, and helminthicidal time of 22.38, 19.43 min, respectively. In contrast, the presence of electron withdrawing chloro group at ortho and para-position of the aromatic ring was found to be favorable for the anthelminthic activity of the compounds 5n and 5o (at concentration of 259.7 μM) with propyl group at the 2-position of the thieno[2,3-d]pyrimidine scaffold, exhibiting mean paralytic time of 2.5 min, 2.81 min and helminthicidal time of 21, 20.03 min, respectively. Anthelmintic activities of these four compounds 5g, 5h, 5n, and 5o (at the concentrations of 284, 261.8, 259.7, and 259.7 μM, respectively) were found to be on par with the standard drug piperazine adipate (time for paralysis and death at 6.25 and 24.5 min, respectively) at concentration of 100 μg/ml (431.03 μM). Overall, the potency of these compounds (5g, 5h, 5n, and 5o) is better than standard drug as they exhibited the same activity at 259.7–284 μM as that of a standard drug (which has shown the same activity at 431.03 μM). Further, the predicted ADME properties of all the synthesized compounds were found to be in the satisfactory ranges as predicted by SwissADME software and found to have drug-like properties. Thus, further modification of these compounds might lead to the discovery of more potent analogs.

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Acknowledgements

Authors thank Sri K.V. Vishnu Raju, Chairman-Sri Vishnu Educational Society, Dr. D.B. Raju, Director and Dr. K. Prasad, Principal-Shri Vishnu College of Pharmacy for their constant support and encouragement. They also thank Lila Impex Ltd for spectral and elemental analysis.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Shri Vishnu College of Pharmacy, Vishnupur, West Godavari Dist., Bhimavaram, AP, 534 202, India

    Satya Sri Chitikina, Praveen Buddiga & Raghu Prasad Mailavaram

  2. Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman, 19392, Jordan

    Pran Kishore Deb

  3. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Saudi Arabia

    Katharigatta N. Venugopala & Anroop B. Nair

  4. Department of Biotechnology and Food Technology, Durban University of Technology, Durban, 4001, South Africa

    Katharigatta N. Venugopala

  5. Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid, 21163, Jordan

    Bilal Al-Jaidi

  6. Interdisciplinary Center for Nanotoxicity, Department of Chemistry, Physics and Atmospheric Sciences, Jackson State University, Jackson, MS, 39217, USA

    Supratik Kar

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  1. Satya Sri Chitikina
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Correspondence to Raghu Prasad Mailavaram.

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Chitikina, S.S., Buddiga, P., Deb, P.K. et al. Synthesis and anthelmintic activity of some novel (E)-2-methyl/propyl-4-(2-(substitutedbenzylidene)hydrazinyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines. Med Chem Res 29, 1600–1610 (2020). https://doi.org/10.1007/s00044-020-02586-5

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